Publications by authors named "Rashid Mir"

72 Publications

Clinical Utility of Amplification Refractory Mutation System-Based PCR and Mutation-Specific PCR for Precise and Rapid Genotyping of Angiotensin-Converting Enzyme 1 (ACE1-rs4646996 D>I) and Angiotensin-Converting Enzyme 2 (ACE2-rs4240157T>C) Gene Variations in Coronary Artery Disease and Their Strong Association with Its Disease Susceptibility and Progression.

Diagnostics (Basel) 2022 May 26;12(6). Epub 2022 May 26.

Prince Fahd Bin Sultan Research Chair, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia.

Experimental clinical and research studies demonstrated that the renin-angiotensin system (RAS) affects the pathogenesis of atherosclerosis and the prognosis of coronary heart disease (CHD). The results show that ACE2 (angiotensin I-converting enzyme 2) might act as a protective protein for cardiovascular diseases; however, only a few studies in human populations have been carried out. The aim of this study was to develop, optimize, and validate a direct T-ARMS-based PCR assay for the precise and rapid genotyping of ACE1-rs4646996 D>I and ACE2-rs4240157T>C and study their association with coronary artery disease susceptibility and progression. This study included 149 consecutive coronary artery disease patients and 150 healthy controls. We utilized T-ARMS for the precise and rapid genotyping of ACE2-rs4240157; rs4646994. Our results indicated that the ACE1-rs4646996 D>I genotypes observed between CAD cases and controls were statistically significant ( < 0.008) and, similarly, the ACE2-rs4240157T>C genotypes observed were significant ( < 0.0001). Moreover, the frequency of the D allele (ACE1-D>I) and C allele (ACE2-rs4240157T>C) was found to be higher among CAD patients than the HC. Our results indicated that in the codominant model, the ACE2-ID genotype was strongly associated with increased CAD susceptibility in a codominant model with an OR of 2.37, (95%) CI = (1.023-5.504), and < 0.04. Similarly, the ACE2-DD genotype was strongly associated with an increased CAD susceptibility with an OR of 3.48, (95%) CI = (1.49 to 8.117), and < 0.003. Similarly, in allelic comparison, the D allele was strongly associated with CAD susceptibility with an OR of 1.59, (95%) CI = (1.12-2.24), and < 0.003. Our results revealed that there was a significant correlation between ACE2-I/D genotypes and hypertension, T2D, and obesity ( < 0.05). The results of ACE2 rs4240157 genotyping indicated a strong association in the codominant model with an increased CAD susceptibility with an OR of 3.62, (95%) CI = (2.027 to 6.481), and < 0.0001. Similarly, in a dominant inheritance model, a strong association is observed between the ACE2 rs4240157 (CT+CC) genotype with an OR of 6.34, (95%) CI = (3.741 to 10.749), and < 0.0001. In allelic comparison, the T allele was strongly associated with CAD susceptibility with an OR of 5.56, (95% CI = (3.56 to 7.17), and < 0.0001. Similarly, our results revealed that there was a significant association of the ACE2-rs4240157T>C genotypes with Triglycerides (mg/dL), HDL-C (mg/dL), total Cholesterol (mg/dL), and C-reactive protein (mg/L) in CAD. It was indicated that the ARMS technique and MS-PCR assay proved to be fast, accurate, and reliable for ACE2-rs4240157T>C and ACE1-rs4646996 D>I, respectively, and can be used as a potential molecular tool in the diagnosis of genetic diseases in undeveloped and developing countries-where there might be a shortage of medical resources and supplies. ACE1-I>D genotypes were strongly associated with T2D, hypertension, and obesity ( < 0.002). Besides the ACE2-rs4240157 CT heterozygosity genotype, the T allele was strongly associated with CAD susceptibility. Future longitudinal studies in different ethnic populations with larger sample sizes are recommended to validate these findings.
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http://dx.doi.org/10.3390/diagnostics12061321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9222124PMC
May 2022

Molecular Determination of Vascular Endothelial Growth Factor, miRNA-423 Gene Abnormalities by Utilizing ARMS-PCR and Their Association with Fetal Hemoglobin Expression in the Patients with Sickle Cell Disease.

Curr Issues Mol Biol 2022 Jun 1;44(6):2569-2582. Epub 2022 Jun 1.

Department of Pharmacology and Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 16278, Saudi Arabia.

Recent studies have indicated that microRNA and VEGF are considered to be genetic modifiers and are associated with elevated levels of fetal haemoglobin HbF, and thus they reduce the clinical impact of sickle haemoglobin (HbS) patients. This cross-sectional study was performed on clinical confirmed subjects of SCD cases. miR-423-rs6505162 C>T and VEGF-2578 C>A genotyping was conducted by ARMS-PCR in SCD and healthy controls. A strong clinical significance was reported while comparing the association of miR-423 C>T genotypes between SCD patients and controls ( = 0.031). The microRNA-423 AA genotype was associated with an increased severity of SCD in codominant model with odd ratio (OR = 2.36, 95% CI, (1.15-4.84), = 0.018) and similarly a significant association was observed in recessive inheritance model for microRNA-423 AA vs (CC+CA) genotypes (OR = 2.19, 95% CI, (1.32-3.62), < 0.002). The A allele was associated with SCD severity (OR = 1.57, 95% CI, (1.13-2.19), < 0.007). The distribution of VEGF-2578 C>A genotypes between SCD patients and healthy controls was significant ( < 0.013). Our results indicated that in the codominant model, the VEGF-2578-CA genotype was strongly associated with increased SCD severity with OR = 2.56, 95% CI, (1.36-4.82), < 0.003. The higher expression of HbA1 (65.9%), HbA2 (4.40%), was reported in SCD patients carrying miR-423-AA genotype than miR-423 CA genotype in patients carrying miR-423 CA genotype HbA1 (59.98%), HbA2 (3.74%) whereas patients carrying miR-423 CA genotype has higher expression of HbF (0.98%) and HbS (38.1%) than in the patients carrying AA genotype HbF (0.60%), HbS (36.1%). ARMS-PCR has been proven to be rapid, inexpensive and is highly applicable to gene mutation screening in laboratories and clinical practices. This research highlights the significance of elucidating genetic determinants that play roles in the amelioration of the HbF levels that is used as an indicator of severity of clinical complications of the monogenic disease. Further well-designed studies with larger sample sizes are necessary to confirm our findings.
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http://dx.doi.org/10.3390/cimb44060175DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9221959PMC
June 2022

Targeting cancer signaling pathways by natural products: Exploring promising anti-cancer agents.

Biomed Pharmacother 2022 Jun 30;150:113054. Epub 2022 Apr 30.

Laboratory of Molecular and Metabolic Imaging, Sidra Medicine, Doha, Qatar. Electronic address:

Cancer is one of the leading causes of death and significantly burdens the healthcare system. Due to its prevalence, there is undoubtedly an unmet need to discover novel anticancer drugs. The use of natural products as anticancer agents is an acceptable therapeutic approach due to accessibility, applicability, and reduced cytotoxicity. Natural products have been an incomparable source of anticancer drugs in the modern era of drug discovery. Along with their derivatives and analogs, natural products play a major role in cancer treatment by modulating the cancer microenvironment and different signaling pathways. These compounds are effective against several signaling pathways, mainly cell death pathways (apoptosis and autophagy) and embryonic developmental pathways (Notch pathway, Wnt pathway, and Hedgehog pathway). The historical record of natural products is strong, but there is a need to investigate the current role of natural products in the discovery and development of cancer drugs and determine the possibility of natural products being an important source of future therapeutic agents. Many target-specific anticancer drugs failed to provide successful results, which accounts for a need to investigate natural products with multi-target characteristics to achieve better outcomes. The potential of natural products to be promising novel compounds for cancer treatment makes them an important area of research. This review explores the significance of natural products in inhibiting the various signaling pathways that serve as drivers of carcinogenesis and thus pave the way for developing and discovering anticancer drugs.
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http://dx.doi.org/10.1016/j.biopha.2022.113054DOI Listing
June 2022

Differential Association of Selected Adipocytokines, Adiponectin, Leptin, Resistin, Visfatin and Chemerin, with the Pathogenesis and Progression of Type 2 Diabetes Mellitus (T2DM) in the Asir Region of Saudi Arabia: A Case Control Study.

J Pers Med 2022 May 1;12(5). Epub 2022 May 1.

Department of Family medicine, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.

Background: Sedentary lifestyles, urbanization and improvements in socio-economic status have had serious effects on the burden of diabetes across the world. Diabetes is one of the 10 leading causes of death globally, and individuals with diabetes have a 2-3-fold increased risk of all-cause mortality. Adipose tissue is increasingly understood as a highly active endocrine gland that secretes many biologically active substances, including adipocytokines. However, the exact and discrete pathophysiological links between obesity and T2DM are not yet fully elucidated.

Methods: In the current study, we present the association of five diverse adipocytokines, adiponectin, leptin, resistin, visfatin and chemerin, with T2DM in 87 patients (46 males and 41 females) with type 2 diabetes mellitus and 85 healthy controls (44 males and 41 females) from the Asir region of Saudi Arabia. The patients were divided into four groups: normal BMI, overweight, obese and severely obese. The baseline biochemical characteristics, including HbA1c and anthropometric lipid indices, such as BMI and waist-hip ratio, were determined by standard procedures, whereas the selected adipokine levels were assayed by ELISA.

Results: The results showed significantly decreased levels of adiponectin in the T2DM patients compared to the control group, and the decrease was more pronounced in obese and severely obese T2DM patients. Serum leptin levels were significantly higher in the females compared to the males in the controls as well as all the four groups of T2DM patients. In the male T2DM patients, a progressive increase was observed in the leptin levels as the BMI increased, although these only reached significantly altered levels in the obese and severely obese patients. The serum leptin levels were significantly higher in the severely obese female patients compared to the controls, patients with normal BMI, and overweight patients. The leptin/adiponectin ratio was significantly higher in the obese and severely obese patients compared to the controls, patients with normal BMI, and overweight patients in both genders. The serum resistin levels did not show any significant differences between the males and females in thr controls or in the T2DM groups, irrespective of the BMI status of the T2DM patients. The visfatin levels did not reveal any significant gender-based differences, but significantly higher levels of visfatin were observed in the T2DM patients, irrespective of their level of obesity, although the higher values were observed in the obese and highly obese patients. Similarly, the serum chemerin levels in the controls, as well as in T2DM patients, did not show any significant gender-based differences. However, in the T2DM patients, the chemerin levels showed a progressive increase, with the increase in BMI reaching highly significant levels in the obese and severely obese patients, respectively.

Conclusion: In summary, it is concluded that significantly altered concentrations of four adipokines, adiponectin, leptin, visfatin and chemerin, were found in the T2DM patient group compared to the controls, with more pronounced alterations observed in the obese and highly obese patients. Thus, it can be surmised that these four adipokines play a profound role in the onset, progression and associated complications of T2DM. In view of the relatively small sample size in our study, future prospective studies are needed on a large sample size to explore the in-depth relationship between adipokines and T2DM.
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http://dx.doi.org/10.3390/jpm12050735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9143828PMC
May 2022

Differential impact of the angiotensin-converting enzyme-2 (ACE2 rs4343 G>A) and miR-196a2 rs11614913 C>T gene alterations in COVID-19 disease severity and mortality.

Exp Ther Med 2022 Jun 29;23(6):418. Epub 2022 Apr 29.

Department of Family Medicine, College of Medicine, University of Bisha, Bisha 61922, Saudi Arabia.

The recent coronavirus outbreak from Wuhan China in late 2019 caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in a global pandemic of coronavirus-19 disease (COVID-19). Understating the underlying mechanism of the pathogenesis of coronavirus infection is important not only because it will help in accurate diagnosis and treatment of the infection but also in the production of effective vaccines. The infection begins when SARS-CoV-2 enters the cells through binding of its envelope glycoprotein to angiotensin-converting enzyme2 (ACE2). Gene variations of ACE2 and microRNA (miR)-196 are associated with viral infection and other diseases. The present study investigated the association of the ACE2 rs4343 G>A and miR-196a2 rs11614913 C>T gene polymorphisms with severity and mortality of COVID-19 using amplification refractory mutation system PCR in 117 COVID-19 patients and 103 healthy controls from three regions of Saudi Arabia. The results showed that ACE2 rs4343 GA genotype was associated with severity of COVID-19 (OR=2.10, P-value 0.0028) and ACE2 rs4343 GA was associated with increased mortality with OR=3.44, P-value 0.0028. A strong correlation between the ACE2 rs4343 G>A genotype distribution among COVID-19 patients was reported with respect to their comorbid conditions including sex (P<0.023), coronary artery disease (P<0.0001), oxygen saturation <60 mm Hg (P<0.0009) and antiviral therapy (0.003). The results also showed that the CT genotype and T allele of the miR-196a2 rs11614913 C>T were associated with decreased risk to COVID-19 with OR=0.76, P=0.006 and OR=0.54, P=0.005, respectively. These results need to be validated with future molecular genetic studies in a larger sample size and different populations.
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http://dx.doi.org/10.3892/etm.2022.11345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9117950PMC
June 2022

Clinical Implications of Glyoxalase1 Gene Polymorphism and Elevated Levels of the Reactive Metabolite Methylglyoxal in the Susceptibility of Type 2 Diabetes Mellitus in the Patients from Asir and Tabuk Regions of Saudi Arabia.

J Pers Med 2022 Apr 15;12(4). Epub 2022 Apr 15.

Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Shaqra 11961, Saudi Arabia.

Diabetes mellitus constitutes a big challenge to the global health care system due to its socioeconomic impacts and very serious complications. The incidence and the prevalence rate are increased in the Gulf region including the KSA. Type 2 diabetes mellitus (T2DM) is caused by diverse risk factors including obesity, unhealthy dietary habits, physical inactivity, smoking and genetic factors. The molecular genetic studies have helped in the detection of many single nucleotide polymorphisms (SNP) with different diseases including cancers, cardiovascular diseases and T2DM. The glyoxalase 1 (GLO1) is a detoxifying enzyme and catalyzes the elimination of the cytotoxic product methylglyoxal (MG) by converting it to D-lactate, which is not toxic to tissues. MG accumulation is associated with the pathogenesis of different diseases including T2DM. In this study, we have investigated the association of the glyoxalase 1 SNPs (rs2736654) rs4746 C>A and rs1130534 T>A with T2DM using the amplification refractory mutation system PCR. We also measured the concentration of MG by ELISA in T2DM patients and matched heathy controls. Results show that the CA genotype of the GLO rs4647 A>C was associated with T2DM with OR = 2.57, -value 0.0008 and the C allele was also associated with increased risk to T2DM with OR = 2.24, -value = 0.0001. It was also observed that AT genotype of the rs1130534 was associated with decreased susceptibility to T2DM with OR = 0.3, -value = 0.02. The A allele of rs1130534 was also associated with reduced risk to T2DM with PR = 0.27 = 0.006. In addition, our ELISA results demonstrate significantly increased MG concentrations in serum of the T2DM patients. We conclude that the GLO1 SNP may be associated with decreased enzyme activity and a resultant susceptibility to T2DM. Further well-designed studies in different and large patient populations are recommended to verify these findings.
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http://dx.doi.org/10.3390/jpm12040639DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030104PMC
April 2022

Clinical Implications of Krüpple-like Transcription Factor KLF-14 and Certain Micro-RNA (miR-27a, miR-196a2, miR-423) Gene Variations as a Risk Factor in the Genetic Predisposition to PCOS.

J Pers Med 2022 Apr 6;12(4). Epub 2022 Apr 6.

Faculty of Applied Medical Science, University of Tabuk, Tabuk 71491, Saudi Arabia.

Polycystic ovary syndrome (PCOS) is a disorder with a symptomatic manifestation of an array of metabolic and endocrine impairments. PCOS has a relatively high prevalence rate among young women of reproductive age and is a risk factor for some severe metabolic diseases such as T2DM, insulin insensitivity, and obesity, while the most dominant endocrine malfunction is an excess of testosterone showing hyperandrogenism and hirsutism. MicroRNAs have been implicated as mediators of metabolic diseases including obesity and insulin resistance, as these can regulate multiple cellular pathways such as insulin signaling and adipogenesis. Genome-wide association studies during the last few years have also linked the Krüpple-like family of transcription factors such as KLF14, which contribute in mechanisms of mammalian gene regulation, with certain altered metabolic traits and risk of atherosclerosis and type-2 DM. This study has characterized the biochemical and endocrine parameters in PCOS patients with a comprehensive serum profiling in comparison to healthy controls and further examined the influence of allelic variations for miRNAs 27a (rs895819 A > G), 196a2 (rs11614913 C > T), 423 (rs6505162C > A), and transcription factor KLF14 (rs972283 A > G) gene polymorphism on the risk and susceptibility to PCOS. The experimental protocol included amplification refractory mutation-specific (ARMS)-PCR to detect and determine the presence of these polymorphic variants in the study subjects. The results in this case-control study showed that most of the serum biomarkers, both biochemical and endocrine, that were analyzed in the study demonstrated statistically significant alterations in PCOS patients, including lipids (LDL, HDL, cholesterol), T2DM markers (fasting glucose, free insulin, HOMA-IR), and hormones (FSH, LH, testosterone, and progesterone). The distribution of Krüppel-like factor 14 rs972283 G > A, miR-27a rs895819 A > G, and miR-196a-2 rs11614913 C > T genotypes analyzed within PCOS patients and healthy controls in the considered population was significant ( < 0.05), except for miR-423 rs6505162 C > A genotypes ( > 0.05). The study found that in the codominant model, KLF14-AA was strongly associated with greater PCOS susceptibility (OR 2.35, 95% CI = 1.128 to 4.893, < 0.022), miR-27a-GA was linked to an enhanced PCOS susceptibility (OR 2.06, 95% CI = 1.165 to 3.650, < 0.012), and miR-196a-CT was associated with higher PCOS susceptibility (OR 2.06, 95% CI = 1.191 to 3.58, < 0.009). Moreover, allele A of KLF-14 and allele T of miR-196a2 were strongly associated with PCOS susceptibility in the considered population.
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http://dx.doi.org/10.3390/jpm12040586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9030665PMC
April 2022

Aberrant hydroxymethylation in promoter CpG regions of genes related to the cell cycle and apoptosis characterizes advanced chronic myeloid leukemia disease, poor imatinib respondents and poor survival.

BMC Cancer 2022 Apr 14;22(1):405. Epub 2022 Apr 14.

Department of Biochemistry, Multidisciplinary Research Unit (MRU), Maulana Azad Medical College, New Delhi, India.

Background: There is strong evidence that disease progression, drug response and overall clinical outcomes of CML disease are not only decided by BCR/ABL1 oncoprotein but depend on accumulation of additional genetic and epigenetic aberrations. DNA hydroxymethylation is implicated in the development of variety of diseases. DNA hydroxymethylation in gene promoters plays important roles in disease progression, drug response and clinical outcome of various diseases. Therefore in this study, we aimed to explore the role of aberrant hydroxymethylation in promoter regions of different tumor suppressor genes in relation to CML disease progression, response to imatinib therapy and clinical outcome.

Methods: We recruited 150 CML patients at different clinical stages of the disease. Patients were followed up for 48 months and haematological/molecular responses were analysed. Haematological response was analysed by peripheral blood smear. BCR/ABL1 specific TaqMan probe based qRT-PCR was used for assessing the molecular response of CML patients on imatinib therapy. Promoter hydroxymethylation of the genes was characterized using MS-PCR.

Results: We observed that promoter hydroxymethylation of DAPK1, RIZ1, P16INK4A, RASSF1A and p14ARF genes characterize advanced CML disease and poor imatinib respondents. Although, cytokine signalling (SOCS1) gene was hypermethylated in advanced stages of CML and accumulated in patients with poor imatinib response, but the differences were not statistically significant. Moreover, we found hypermethylation of p14, RASSF1 and p16 genes and cytokine signalling gene (SOCS1) significantly associated with poor overall survival of CML patients on imatinib therapy. The results of this study are in agreement of the role of aberrant DNA methylation of different tumor suppressor genes as potential biomarkers of CML disease progression, poor imatinib response and overall clinical outcome.

Conclusion: In this study, we report that promoter hydroxymethylation of DAPK1, RIZ1, P16INK4A, RASSF1A and p14ARF genes is a characteristic feature of CML disease progressions, defines poor imatinib respondents and poor overall survival of CML patients to imatinib therapy.
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http://dx.doi.org/10.1186/s12885-022-09481-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9008925PMC
April 2022

Severe COVID-19 Pneumonia and Genetic Susceptibility: A Case Report and Literature Review.

Cureus 2022 Mar 30;14(3):e23636. Epub 2022 Mar 30.

Molecular Oncology, Genetics and Translational Medicine, Faculty of Applied Medical Sciences, Tabuk, SAU.

Genetic susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) morbidity and mortality continues to evolve. This report presents a case of an apparently healthy male adult who developed severe coronavirus disease 2019 (COVID-19) and a study on relevant genetic mutations, namely, angiotensin-converting enzyme 2 (ACE2-rs4646994 I/D) gene, glutathione S-transferase (GST) M1 and T1 gene, and miR-423 rs6505162 C>A gene polymorphism. Results showed that the ACE-DD genotype of ACE2, (GSTM1+/+) (GSTT1-/-) genotype of GST gene, and CA genotype (heterozygosity) of miR-423 rs6505162 genes, which were found in the patient, could be independent risk factors of severe COVID-19, even without comorbidities.
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http://dx.doi.org/10.7759/cureus.23636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8971094PMC
March 2022

Potential impact of , and gene abnormalities on the development and progression of type 2 diabetes mellitus in Asir and Tabuk regions of Saudi Arabia.

Mol Med Rep 2022 May 16;25(5). Epub 2022 Mar 16.

Department of Family Medicine, College of Medicine, University of Bisha, Bisha 61922, Kingdom of Saudi Arabia.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by persistent hyperglycemia and is associated with serious complications. The risk factors for T2DM include both genetic and lifestyle factors. Genome‑wide association studies have indicated the association of genetic variations with many diseases, including T2DM. Glucokinase (GCK) plays a key role in the regulation of insulin release in the pancreas and catalyzes the first step in glycolysis in the liver. Genetic alterations in the gene have been implicated in both hyperglycemia and hypoglycemia. MicroRNAs (miRNAs/miRs) are small non‑coding RNA molecules that are involved in the important physiological processes including glucose metabolism. In the present study, the association of the single nucleotide polymorphisms (SNPs) in the , and genes with susceptibility to T2DM in patients from two regions of Saudi Arabia were examined, using the tetra‑primer amplification refractory mutation system. The results showed that the AA genotype and the A allele of GCK rs1799884 were associated with T2DM [odds ratio (OR)=2.25, P=0.032 and OR=1.55, P=0.021, respectively]. Likewise, the CT genotype and T allele of rs11614913 were associated with an increased risk of T2DM (OR=2.36, P=0.0059 and OR=1.74, P=0.023, respectively). In addition, the CA genotype of rs6505162 C>A was found to be linked with T2DM (OR=2.12 and P=0.021). It was concluded in the present research study that gene variations in , and are potentially associated with an increased risk of T2DM. These results, in the future, may help in the identification and stratification of individuals susceptible to T2DM. Future longitudinal studies with larger sample sizes and in different ethnic populations are recommended to validate these findings.
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http://dx.doi.org/10.3892/mmr.2022.12675DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8941532PMC
May 2022

Biochemical Characterization and Molecular Determination of Estrogen Receptor-α (ESR1 PvuII-rs2234693 T>C) and MiRNA-146a (rs2910164 C>G) Polymorphic Gene Variations and Their Association with the Risk of Polycystic Ovary Syndrome.

Int J Environ Res Public Health 2022 03 6;19(5). Epub 2022 Mar 6.

Faculty of Applied Medical Science, University of Tabuk, Tabuk 71491, Saudi Arabia.

Polycystic ovary syndrome (PCOS) is regarded as one of the most frequently encountered endocrine disorders and affects millions of young women worldwide, resulting in an array of complex metabolic alterations and reproductive failure. PCOS is a risk factor for diabetes mellitus, obstructive sleep apnea, obesity and depression in patients. Estrogen receptors (ESRs) are significant candidates in endocrine function and ovarian response in women. Moreover, microRNAs and long non-coding RNAs are emerging as principal mediators of gene expression and epigenetic pathways in various disease states. This study has characterized the clinical parameters in PCOS patients with comprehensive biochemical profiling compared to healthy controls and further examined the influence of allelic variations for estrogen receptor-α (ESR1 PvuII-rs2234693 T>C) and miRNA-146a (rs2910164 C>G) gene polymorphism on the risk of and susceptibility to PCOS. In this case-control study, we have used amplification refractory mutation specific (ARMS)-PCR to detect and determine the presence of these polymorphic variants in the study subjects. Our results demonstrated that most of the biochemical markers, which were analyzed in the study, show statistically significant alterations in PCOS patients, including fasting glucose, free insulin, HOMA-IR, LDL, HDL, cholesterol and hormones such as FSH, LH, testosterone and progesterone, which correlate with the established biochemical alterations in the disorder. Further, it is reported that for estrogen receptor-α (ESR1 PvuII-rs2234693 T>C), the frequency of the T allele (fT) was significantly higher among patients (0.64 vs. 0.44) compared to controls, while the frequency of the C allele (fC) was lower in patients (0.36 vs. 0.56) compared to controls. However, it was found that there was no association of an increased risk of PCOS with the ESR1 PvuII-rs2234693 C>T gene polymorphism. On the contrary, the study found strong association of miRNA-146a (rs2910164 C>G) gene polymorphism with an enhanced risk of PCOS. The frequency of the C allele (fC) was significantly higher among patients (0.52 vs. 0.36) compared to controls. The frequency of the G allele (fG) was found to be lower in patients (0.48 vs. 0.64) compared to controls. The codominant, dominant and recessive models display a statistically significant association of polymorphic variations with PCOS. Moreover, the G allele was associated strongly with PCOS susceptibility with an OR = 1.92 (95%) CI = (1.300-2.859), RR = 1.38 (1.130-1.691) -value < 0.001.
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http://dx.doi.org/10.3390/ijerph19053114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8910123PMC
March 2022

Ionized Blood Magnesium in Sick Children: An Overlooked Electrolyte.

J Trop Pediatr 2022 02;68(2)

Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Kingdom of Saudi Arabia.

Introduction: Magnesium is a less frequently monitored electrolyte in critically ill patients. Hypomagnesemia is associated with increased need for mechanical ventilation, mortality and prolonged ICU stay. The present study was undertaken to identify the proportion of children with abnormal magnesium levels and correlate it with disease outcome.

Methods: This observational study included children aged 1 month to 12 years hospitalized at the emergency room. Heparinized blood was collected for determination of ionized magnesium, ionized calcium, sodium, potassium and lactate using Stat Profile Prime Plus (Nova Biomedical, Waltham, MA, USA). Clinical outcomes for duration of hospitalization, and death or discharge were recorded.

Results: A total of 154 (102 males) children with median (IQR) age of 11 (4, 49.75) months were enrolled. Sixty one (39.6%) had ionized magnesium levels below 0.42 mmol/l, 63 (40.9%) had normal levels and 30 (19.4%) had hypermagnesemia (>0.59 mmol/l). Hypomagnesemia was associated with hypocalcemia (p < 0.001), hyponatremia (p < 0.001) and hypokalemia (p < 0.02). A higher proportion of children with hypermagnesemia required ventilation than hypomagnesemia (26% vs. 9%) and succumbed (35% vs. 20%), respectively; p > 0.05. Ninety-three (60.3%) had hypocalcemia and 10 (6.5%) children had hypercalcemia. There was good correlation between ionized calcium and magnesium values (r = 0.72, p < 0.001).

Conclusion: Both hypomagnesemia and hypermagnesemia were seen in critically ill children. Patients with hypomagnesemia had significantly higher proportion of other electrolyte abnormalities.
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http://dx.doi.org/10.1093/tropej/fmac022DOI Listing
February 2022

On the role of Inflammatory and cytokine biomarkers in the pathogenesis of Frailty Syndrome.

Endocr Metab Immune Disord Drug Targets 2022 Mar 4. Epub 2022 Mar 4.

Department of Medical Lab Technology, Faculty of Applied Medical Sciences, Prince Fahd Bin Sultan Research chair, University of Tabuk, Tabuk 71491, Saudi Arabia.

Frailty is a conglomerated elderly disorder that includes multiple abnormalities like anemia; subjection to increased titer of catabolic hormones; compromised physiology of most of the body systems. Many studies have established the biomarkers that correlate with physical function and immune aging, but, people can age differently, so chronological age is not a sufficient marker of susceptibility to disabilities, morbidities, and mortality. The pathophysiology of frailty is not clearly understood, but a critical role of an enhanced inflammation in the body is hypothesized. Many factors contribute to the development of frailty syndrome such as pro-inflammatory cytokines, inflammatory markers, inflammatory cytokines and secosteroids like vitamin D. This review aims to highlight the role of Inflammatory and cytokine biomarkers and vitamin D in the pathogenesis of Frailty Syndrome.
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http://dx.doi.org/10.2174/1871530322666220304220522DOI Listing
March 2022

Clinical Correlations of Lipid Profiles with the Age and Gender in the Coronary Artery Disease Patients: A Study of 3878 CAD Patients from India.

Endocr Metab Immune Disord Drug Targets 2022 ;22(4):440-452

Sri Jayadeva Institute of Cardiovascular Science & Research, Bangalore, India.

Background: Cardiovascular diseases (CVDs) are crucial cause of death and hospitalization all over the world including India. The CVDs including the coronary artery disease (CAD) are developed by the interaction of genetic and environmental factors. Hyperlipidemia is a traditional risk factor for CVD.

Aim: The aim of this study was to study the clinical correlations of lipid profiles with the age and gender in the Coronary Artery Disease Patients: Methods: In this study, we have investigated the effect of age and sex on in lipid profile in 3878 (1171 females and 2707 males) CAD patients from India.

Results: The plasma TG was higher in males than in females regardless of the age. Results showed that CAD female patients had significantly increased HDL-C than their aged matched males. Moreover, the plasma TC and LDL-C were significantly higher in males than females until age 40 years. Then after the age of 40 years, TC and LDL-C become significantly higher in females than in males. In addition, we found that more than 85% of CAD cases were <55 years old, and about 30% of CAD cases had normal lipid profile.

Conclusion: We conclude that elderly females are at a greater risk for CAD than males. Moreover, there were no significant differences in CVDs causes between nonelderly and elderly females. In addition, a higher percentage of cases were premature CAD, and 30% of CAD may be caused by loci that are not related to lipid metabolism.
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http://dx.doi.org/10.2174/1871530322666220304110306DOI Listing
May 2022

Molecular determination of progesterone receptor's PROGINS allele (Alu insertion) and its association with the predisposition and susceptibility to polycystic ovary syndrome (PCOS).

Mamm Genome 2022 Sep 8;33(3):508-516. Epub 2022 Jan 8.

Prince Fahd Research Chair, Faculty of Applied Medical Science, University of Tabuk, Tabuk, Saudi Arabia.

Polycystic ovary syndrome, previously known as Stein-Leventhal syndrome, is associated with altered reproductive endocrinology, predisposing a young woman towards the risk of PCOS. It has a prevalence of 6-20% among the reproductive-age women. Progesterone is a key hormone in the pathophysiology of PCOS and patients show diminished response (progesterone resistance), implicating the role of progesterone receptor (PR) as a factor in the disease etiology and prognosis. In this case-control study, we have used mutation-specific PCR (confirmed by Sanger sequencing) to detect the presence of a pathologically significant PR polymorphic variant called as PROGINS. The variant has an Alu insertion in intron G and has two SNPs in exon 4 and exon 5, with all the three aberrations in complete disequilibrium. Our results demonstrated a statistically significant difference in the frequencies of PROGINS between the PCOS patients and healthy controls (p = 0.047). The frequencies of the genotypes CC (A1/A1), CT (A1/A2), and TT (A2/A2) in patients were 74.50%, 20.58%, and 4.90%, and in healthy controls they were 87.28%, 11%, and 1.69%, respectively. Our results put forward two determining factors with regard to PCOS: (i) the frequency of PROGINS allele was significantly higher among PCOS patients compared to the healthy matched controls (0.15 vs 0.07) in the studied population, (ii) the PROGIN allele was significantly associated with the lower levels of serum progesterone in PCOS patients (p < 0.003). The findings are conspicuous as these relate the PROGINS variant to the increased susceptibility of PCOS and might explain the progesterone resistance in patients.
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http://dx.doi.org/10.1007/s00335-021-09941-wDOI Listing
September 2022

Biological and Clinical Implications of TNF-α Promoter and CYP1B1 Gene Variations in Coronary Artery Disease Susceptibility.

Cardiovasc Hematol Disord Drug Targets 2021 ;21(4):266-277

Department of Human Genetics Punjabi University, Punjab,India.

Background: Cardiovascular diseases (CVD) are important causes of death worldwide. Atherosclerosis is a chronic inflammatory disorder. It is the major cause of CVD and is manifested by ischemic heart disease or coronary artery disease (CAD). TNF-α is a pro-inflammatory cytokine that regulates immune response and promotes the development of atherosclerosis. Cytochrome p450 1B1 (CYP1B1) is an enzyme involved in the metabolism of endogenous and exogenous substrates.

Objectives: This study aimed at examining the association of TNF-α rs1800629 G>A and CYP1B1 rs1056827 G>T gene polymorphisms with CAD susceptibility in an Indian cohort.

Methods: AS-PCR and direct DNA sequencing were used to examine the association of TNF-α rs1800629 G >A and CYP1B1 rs1056827 G>T gene polymorphism with CAD in an Indian cohort. A total of 100 clinically confirmed cases of CAD and 110 matched apparently healthy controls were genotyped.

Results: Allelic and genotypic frequencies did not deviate from Hardy-Weinberg equilibrium in the controls (p>0.05) for TNF-α G-308A and CYP1B1 rs1056827G>A. There was no significant difference between the TNF-α rs1800629 A>G genotype distribution between cases and controls (P-value >0.05). A significant difference was observed between the CYP1B1 rs1056827 G>T genotype distribution between CAD cases and controls (p<0.0003). Our result indicated that in the codominant model, the GA genotype of the CYP1B1 rs1056827 G>T was associated with CAD with OR= 2.21(1.17 to 4.15), RR=1.38(1.07 to 1.78), and p<0.013. In the dominant model, the (GA+AA) genotype was associated with CAD with OR=2.79(1.54 to 5.05) and p<0.007. The CYP1B1 rs1056827 'A' allele was associated with CAD with OR = 2.30 (1.55 to 3.42) and p< 0.0001. Our results indicated that TNF-α 1800629 gene polymorphism was strongly associated with hypercholesteremia (p<0.0009), HDL (p<0.0001), TGL (p<0.039), hypertension (p<0.0001), and smoking (p<0.0001) in patients with Coronary Artery Disease. Similar correlations of CYP1B1 rs1056827 genotypes were reported with cholesterol (p<0.020), HDL (p<0.002), LDL (p<0.006), hypertension (p<0.03), and smoking (p<0.005).

Conclusion: It was reported that the GA genotype of the CYP1B1 rs1056827 G>T was strongly associated with susceptibility to Coronary Artery Disease with OR= 2.21(1.17 to 4.15)) and p<0.013, and similarly, its A allele was associated with predisposition to CAD with OR = 2.30 (1.55 to 3.42) and p< 0.0001. Our results indicated that TNF-α 1800629 gene polymorphism is not associated with predisposition to Coronary Artery Disease. Nevertheless, these results should be taken with caution and further validated with larger-scale studies before being introduced in the clinical setting.
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http://dx.doi.org/10.2174/1871529X22666211221151830DOI Listing
February 2022

Clinical Implications of , and Gene Abnormalities and Their Association with T2D.

Curr Issues Mol Biol 2021 Nov 2;43(3):1859-1875. Epub 2021 Nov 2.

Department of Statistics, Faculty of Science, University of Tabuk, Tabuk 71491, Saudi Arabia.

Type 2 DM (T2D) results from the interaction of the genetic and environmental risk factors. Vascular endothelial growth factor (VEGF), angiotensin I-converting enzyme (ACE), and MicroRNAs (MiRNAs) are involved in important physiological processes. Gene variations in , and genes are associated with diseases. In this study we investigated the associations of the -2578 C/A (rs699947), -2549 insertion/deletion (I/D), and I/D rs4646994 and (rs11888095) gene variations with T2D using the amplification refractory mutation system PCR (ARMS-PCR) and mutation specific PCR (MSP). We screened 122 T2D cases and 126 healthy controls (HCs) for the rs699947, and 133 T2D cases and 133 HCs for the I/D polymorphism. For the ACE I/D we screened 152 cases and 150 HCs, and we screened 129 cases and 112 HCs for the (rs11888095). The results showed that the CA genotype of the VEGF rs699947 and D allele of the I/D polymorphisms were associated with T2D with OR =2.01, -value = 0.011, and OR = 2.42, -value = 0.010, respectively. The result indicated the D allele of the ID was protective against T2D with OR = 0.10, -value = 0.0001, whereas the TC genotype and the T allele of the (rs11888095) were associated with increased risk to T2D with OR = 3.16, -value = 0.0001, and OR = 1.68, -value = 0.01, respectively. We conclude that the (rs699947), I/D and (rs11888095) are potential risk loci for T2D, and that the D allele of the ID polymorphism may be protective against T2D. These results help in identification and stratification for the individuals that at risk for T2D. However, future well-designed studies in different populations and with larger sample sizes are required. Moreover, studies to examine the effects of these polymorphisms on VEGF and ACE proteins are recommended.
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http://dx.doi.org/10.3390/cimb43030130DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8928978PMC
November 2021

Strong Association of Angiotensin Converting Enzyme-2 Gene Insertion/Deletion Polymorphism with Susceptibility to SARS-CoV-2, Hypertension, Coronary Artery Disease and COVID-19 Disease Mortality.

J Pers Med 2021 Oct 27;11(11). Epub 2021 Oct 27.

Department of Family medicine, College of Medicine University of Bisha, Bisha 61922, Saudi Arabia.

Background: The ongoing outbreak of SARS-CoV-2 represents a significant challenge to international health. Several reports have highlighted the importance of ACE2 on the pathogenesis of COVID-19. The spike protein of SARS-CoV-2 efficiently binds to the angiotensin-converting enzyme 2 (ACE2) receptors and facilitates virus entry into the host cell. In the present study, we hypothesize that a functional insertion/deletion polymorphism-rs4646994 I/D and rs4240157 T > C in the ACE gene could be associated with SARS-CoV-2 infection and mortality.

Methodology: This study included 117 consecutive COVID-19 patients and 150 age matched healthy controls (ACE2-rs4646994 I/D) and 100 age matched healthy controls with ACE2 rs4240157 T > C. We used Mutation specific PCR (MSP) for ACE2-rs4646994 I/D genotyping and amplification refractory mutation system (ARMS-PCR) for ACE2 rs4240157 T > C genotyping.

Results: Results indicated that there were significant differences in the genotype distributions of ACE2-rs4646994 I/D polymorphisms ( < 0.030) and ACE2 rs4240157 T > C between COVID-19 patients and controls (-values < 0.05). Higher frequency of DD genotype (48.71%) and D allele (0.67) was reported in COVID-19 patients than controls. Our results showed that the ACE2-DD genotype was strongly associated with increased COVID-19 severity (OR 2.37 (95%) CI = (1.19-4.70), RR = 1.39 (1.09-1.77), < 0.013) and also a strong association was seen with ACE2-ID genotype with COVID-19 severity (OR 2.20 (95%) CI = (1.08-4.46), < 0.020) in the codominant model. In allelic comparison, the D allele was strongly associated with COVID-19 severity (OR 1.58 (95% CI) (1.11-2.27), RR 1.21 (1.05-1.41) < 0.010). A significant correlation of ACE2-I/D genotypes was reported with Age ( < 0.035), T2D ( < 0.0013), hypertension ( < 0.0031) and coronary artery disease ( < 0.0001). Our results indicated ACE2-DD genotype was strongly associated with increased COVID-19 mortality (OR 8.25 (95%) CI = (2.40 to 28.34), < 0.008) and also ACE2-DD + DI genotype was strongly associated with increased COVID-19 mortality with OR 4.74 (95%) CI = (1.5214 to 14.7915), < 0.007. A significant correlation was reported between COVID-19 patients and age matched controls ( < 0.0007). Higher frequency of heterozygosity TC (40%) followed by ACE2-CC genotype (24.78%) was reported among COVID-19 patients. Using multivariate analysis, ACE2-CT genotype was strong associated with SARS-CoV-2 severity with an OR 2.18 (95% CI) (1.92-3.99), < 0.010 and also ACE2-CC genotype was linked with COVID-19 severity with an OR 2.66 (95% CI) (1.53-4.62), < 0.005. A significant correlation of ACE2-T > C genotypes was reported with gender ( < 0.04), T2D ( < 0.035). ACE2-CC genotype was strongly associated with increased COVID-19 mortality OR 3.66 (95%) CI = (1.34 to 9.97), < 0.011 and also ACE2-C allele was associated with COVID-19 mortality OR 2, 01 (1.1761-3.45), < 0.010.

Conclusions: It is concluded that ACE-DD genotype and D allele was strongly associated with increased COVID-19 patient severity. In addition, ACE I/D polymorphism were strongly associated with advanced age, diabetes and ischemic heart disease in COVID-19 patients whereas ACE-II genotype was a protective factor against the development of severe COVID-19. ACE2-DD genotype was strongly associated with increased COVID-19 mortality. Additionally, ACE2-CC and CT genotypes were strongly associated with COVID-19 severity. Therefore, our study might be useful for identifying the susceptible population groups for targeted interventions and for making relevant public health policy decisions.
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http://dx.doi.org/10.3390/jpm11111098DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8621157PMC
October 2021

Molecular Determination of mirRNA-126 rs4636297, Phosphoinositide-3-Kinase Regulatory Subunit 1-Gene Variability rs7713645, rs706713 (Tyr73Tyr), rs3730089 (Met326Ile) and Their Association with Susceptibility to T2D.

J Pers Med 2021 Aug 29;11(9). Epub 2021 Aug 29.

Department of Biochemistry, Govind Ballabh Pant Institute of Postgraduate Medical Education & Research (GIPMER), Associated to Maulana Azad Medical College, Delhi 110002, India.

Type 2 diabetes is a metabolic disease characterized by elevated blood sugar. It has serious complications and socioeconomic impact. The MicroRNAs are short single-stranded and non-coding RNA molecules. They regulate gene expression at the post-transcriptional levels. They are important for many physiological processes including metabolism, growth, and others. The phosphoinositide 3-kinase (PI3K) is important for insulin signaling and glucose uptake. The genome wide association studies have identified the association of certain loci with diseases including T2D. In this study we have examined the association of miR126 rs4636297 and Phosphoinositide-3-kinase regulatory subunit 1 (PIK3R1) gene Variations rs7713645, rs706713 (Tyr73Tyr), and rs3730089 (Met326Ile) with T2D using the amplification refractory mutation system PCR. Results indicated that there was a significant different (-value < 0.05) in the Mir126 rs4636297 genotypes distribution between cases and controls, and the minor allele of the rs4636297 was also associated with T2D with OR = 0.58, -value < 0.05. In addition results showed that there were significant differences (-value < 0.05) of rs4636297 genotype distribution of patients with normal and patient with abnormal lipid profile. Results also showed that the PIK3R1 rs7713645 and rs3730089 genotype distribution was significantly different between cases and controls with a -values < 0.05. In addition, the minor allele of the rs7713645 and rs3730089 were associated with T2D with OR = 0.58, -value < 0.05. We conclude that the Mir126 rs4636297 and PIK3R1 SNPs (rs7713645 and rs3730089) were associated with T2D. These results need verification in future studies with larger sample sizes and in different populations. Protein-protein interaction and enzyme assay studies are also required to uncover the effect of the SNPs on the PI3K regulatory subunit (PI3KR1) and PI3K catalytic activity.
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http://dx.doi.org/10.3390/jpm11090861DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469127PMC
August 2021

Metastatic Breast Cancer, Organotropism and Therapeutics: A Review.

Curr Cancer Drug Targets 2021 ;21(10):813-828

Centre of Research for Development, University of Kashmir, Srinagar 190006, India.

The final stage of breast cancer involves spreading breast cancer cells to the vital organs like the brain, liver lungs and bones in the process called metastasis. Once the target organ is overtaken by the metastatic breast cancer cells, its usual function is compromised causing organ dysfunction and death. Despite the significant research on breast cancer metastasis, it's still the main culprit of breast cancer-related deaths. Exploring the complex molecular pathways associated with the initiation and progression of breast cancer metastasis could lead to the discovery of more effective ways of treating the devastating phenomenon. The present review article highlights the recent advances to understand the complexity associated with breast cancer metastases, organotropism and therapeutic advances.
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http://dx.doi.org/10.2174/1568009621666210806094410DOI Listing
January 2022

Epigenetic Silencing of and Genes by CpG Island Hypermethylation in Epithelial Ovarian Cancer Patients.

Indian J Clin Biochem 2021 Apr 16;36(2):200-207. Epub 2020 May 16.

Department of Biochemistry, Maulana Azad Medical College, New Delhi, 110002 India.

Transcriptional silencing induced by hypermethylation of CpG islands in the promoter regions of genes is believed to be an important mechanism of carcinogenesis in human cancers including epithelial ovarian cancer (EOC). Previously published data on gene methylation of EOC focused mainly on single gene or on cancer tissues. Objectives of the study were to estimate the promoter hypermethylation status of and genes in circulating blood of EOC patients and to determine their association with clinicopathological features of EOC. This case-control study included 50 EOC patients and 20 apparently healthy and age matched female controls. Isolation of genomic DNA was carried out from peripheral venous blood. Methylation in promoter region of and genes was determined by methylation-specific PCR. Methylation of was occurred in 42 out of 50 cases (84.0%) and methylation of gene was occurred in 34 out of 50 cases (68.0%). Methylation of both genes was occurred in 25 cases (50.0%). Occurrence of methylation in and genes was statistically significant ( < 0.0001) in cases compared to controls. Methylation of both genes was not statistically associated with age at diagnosis, menopausal status, histopathological types and FIGO staging of EOC. Identification of the peculiar promoter hypermethylation of and genes might be a successful approach for ancillary diagnosis of EOC at early stage in blood sample.
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http://dx.doi.org/10.1007/s12291-020-00888-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7994475PMC
April 2021

Molecular Evaluation of Exon 8 Cystathionine rs5742905T T>C Gene Polymorphism and Determination of its Frequency, Distribution Pattern, and Association with Susceptibility to Coronary Artery Disease in the North Indian Population.

Cardiovasc Hematol Disord Drug Targets 2021 ;21(2):115-122

Department of Biochemistry, Maulana Azad Medical College, University of Delhi, Delhi, India.

Background: The protein coded by the cystathionine β synthase (CBS) gene acts as a catalyzer and converts homocysteine to cystathionine. Impairment of the CBS gene leads to homocystinuria by cystathionine β synthase deficiency which is linked to Coronary Artery Disease. A number of polymorphisms studies have been performed on the cystathionine β synthase gene. In the current study, we planned to analyze the influence of CBS T833C gene polymorphism(exon 8 cystathionine rs5742905T T>C), its association with Coronary Artery Disease development, and its progression in the north Indian population.

Materials And Methods: The present study comprises 100 angiographically confirmed CAD patients and 100 age and sex-matched healthy controls. A total of 50% or more luminal stenosis at one major coronary artery was considered for the inclusion criteria of the cases. The investigation of T833C polymorphism in the CBS gene was performed by PCR- RFLP technique.

Results: As a result, we found that homozygous mutant (CC) and heterozygous (TC) genotypes of CBS T833C gene polymorphism were significantly higher in CAD patients than in healthy subjects. We also observed a substantially increased CAD risk in dominant, codominant inheritance, and allele-specific models for the CBS T833C gene polymorphism. We analyzed the differential distribution with respect to disease severity, but there was no significant association (p=0.96).

Conclusion: In conclusion, this study demonstrates that CBS T833C gene polymorphism plays a key role in developing coronary artery disease and its progression.
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http://dx.doi.org/10.2174/1871529X21666210315121027DOI Listing
January 2022

Role of Selected miRNAs as Diagnostic and Prognostic Biomarkers in Cardiovascular Diseases, Including Coronary Artery Disease, Myocardial Infarction and Atherosclerosis.

J Cardiovasc Dev Dis 2021 Feb 19;8(2). Epub 2021 Feb 19.

Prince Fahd Bin Sultan Research Chair, Department of Medical Lab Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk 71491, Saudi Arabia.

Cardiovascular diseases are the leading cause of death worldwide in different cohorts. It is well known that miRNAs have a crucial role in regulating the development of cardiovascular physiology, thus impacting the pathophysiology of heart diseases. MiRNAs also have been reported to be associated with cardiac reactions, leading to myocardial infarction (MCI) and ultimately heart failure (HF). To prevent these heart diseases, proper and timely diagnosis of cardiac dysfunction is pivotal. Though there are many symptoms associated with an irregular heart condition and though there are some biomarkers available that may indicate heart disease, authentic, specific and sensitive markers are the need of the hour. In recent times, miRNAs have proven to be promising candidates in this regard. They are potent biomarkers as they can be easily detected in body fluids (blood, urine, etc.) due to their remarkable stability and presence in apoptotic bodies and exosomes. Existing studies suggest the role of miRNAs as valuable biomarkers. A single biomarker may be insufficient to diagnose coronary artery disease (CAD) or acute myocardial infarction (AMI); thus, a combination of different miRNAs may prove fruitful. Therefore, this review aims to highlight the role of circulating miRNA as diagnostic and prognostic biomarkers in cardiovascular diseases such as coronary artery disease (CAD), myocardial infarction (MI) and atherosclerosis.
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http://dx.doi.org/10.3390/jcdd8020022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923109PMC
February 2021

Molecular Evaluation of MicroRNA-146 Gene Variability (rs2910164 C> G) and its Association with Increased Susceptibility to Coronary Artery Disease.

Microrna 2020 ;9(5):363-372

Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia.

Aim: Apart from the modifiable risk factors, genetic factors are believed to influence the outcome of Coronary Artery Diseases (CAD). Under the genetic factors, miRNA polymorphisms, namely Hsa-miR-146a-5p (rs2910164) have become an important tool to study the mechanism that underlies the pathogenesis of this disease. Therefore, we investigated the association of miR-146a gene variations with susceptibility of coronary artery diseases.

Methodology: This study was conducted on 100 CAD patients and 117 matched healthy individuals. Genotyping of the Hsa-miR-146a-5p C>G gene variation was performed by using Amplification Refractory Mutation System PCR method (ARMS-PCR).

Results: The distribution of Hsa-miR-146a-5p rs2910164 C>G genotypes observed between patients and controls was significantly different (P=0.048). Moreover, the frequency of G allele (fG) was found to be significantly higher among patients than in controls (0.36 vs. 0.25). Our findings showed that the Hsa-miR-146a-5p C>G variant was associated with an increased risk of CAD in codominant inheritance model CC vs. CG genotype (OR = 1.84, 95% CI, 1.02-3.31; p=0.040) and (OR = 3.18, 95% CI, 1.02-9.9; p=0.045) for CC vs. GG genotype in dominant inheritance model. Whereas the G allele significantly increased the risk of coronary artery disease (OR =1,81, 95% CI, 1.18-2.78; p=0.006) compared to C allele. Taken together, these results demonstrated that miR-146a/rs2910164 is associated with susceptibility to coronary artery disease, providing novel insights into the genetic etiology and underlying biology of coronary artery disease.

Conclusion: Our findings indicated that Hsa-miR-146a-5p rs2910164 GG genotype and G allele are associated with increased susceptibility to Coronary Artery Disease. A larger sample size can be the key to progress in establishing the genetic co-relation of miRNA gene polymorphisms and cardiovascular diseases.
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http://dx.doi.org/10.2174/2211536609666201209151130DOI Listing
August 2021

Analysis of the Potential Association of Drug-Metabolizing Enzymes and Gene Variations With Type 2 Diabetes: A Case-Control Study.

Curr Drug Metab 2020 ;21(14):1152-1160

Department of Biochemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia.

Background: Cytochrome P450s (CYPs) are drug-metabolizing enzymes catalyzing the metabolism of about 75% of drug in clinical use. CYP2C9 represents 20% CYP proteins in liver cells and is a crucial member of CYPs superfamily. CYP2C19 metabolizes very important drugs such as antiulcer drug omeprazole, the antiplatelet drug clopidogrel and anticonvulsant mephenytoin. Single nucleotide polymorphisms (SNPs) of CYP genes have been associated with unexpected drug reactions and diseases in different populations.

Objective: We examined the associations of CYP2C9*3 (rs1057910) and CYP2C19*3 (rs4986893) with T2D in Saudi population.

Methods: We used the allele-specific PCR (AS-PCR) and DNA sequencing in 111 cases and 104 controls for rs1057910, and in 119 cases and 110 controls for rs4986893.

Results: It is indicated that the genotype distribution of rs1057910 in cases and controls were not significantly different (P=0.0001). The genotypes of rs1057910 were not associated with type 2 diabetes (T2D) (P>0.05). Whereas the genotype distribution of rs4986893 in cases and controls was significantly different (P=0.049). The AA genotype of rs4986893 may be associated in increased risk to T2D with OR=17.25 (2.06-143.8), RR=6.14(0.96-39.20), P=0.008.

Conclusion: The CYP2C9*3 (rs1057910) may not be associated with T2D, while CYP2C19*3 (rs4986893) is probably associated with T2D. These findings need to be validated in follow-up studies with larger sample sizes and different populations.
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http://dx.doi.org/10.2174/1389200221999201027200931DOI Listing
October 2021

Reply to Comment: Evaluation of the Association of Omentin 1 rs2274907 A > T and rs2274908 G > A Gene Polymorphisms with Coronary Artery Disease in Indian Population: A Case-Control Study.

J Pers Med 2020 Oct 26;10(4). Epub 2020 Oct 26.

Department of Human Genetics, Punjabi University, Punjab 147002, India.

Coronary artery disease (CAD) is a major cause of death all over the world. CAD is caused by atherosclerosis which is induced by the interaction of genetic factors and environmental factors. Genome-wide association studies have revealed the association of certain gene polymorphisms with susceptibility to CAD. Omentin 1 is an adipokine secreted by the visceral adipose tissues and has been reported to have anti-inflammatory, cardioprotective, and enhances insulin sensitivity. In this study, we examined the role of omentin-1 common single nucleotide polymorphisms (SNPs) (rs2274907 A > T and rs2274908 G > A) in CAD. We conclude that the AT genotype and the T allele of the rs2274907 A > T is associated with Cad in the south Indian population. Our results indicated that the rs2274907 SNP may be associated with CAD in this population. This finding needs further validation in well-designed and large-sample size studies before being introduced in clinical settings.
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http://dx.doi.org/10.3390/jpm10040194DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711485PMC
October 2020

Molecular Evaluation of HIF-1α Gene Variation and Determination of Its Frequency and Association with Breast Cancer Susceptibility in Saudi Arabia.

Endocr Metab Immune Disord Drug Targets 2021 ;21(3):544-553

Prince Fahd Bin Sultan Research Chair, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, University of Tabuk, Tabuk, Saudi Arabia.

Aim: Hypoxia-inducible factor 1 (HIF-1α) is responsible in regulating oxygen homeostasis in tissues and is a central effector of the hypoxic response besides its protein overexpression has been shown to have prognostic relevance in several cancers including breast cancer. Several reports indicated that HIF-1α gene variation C1772T (Pro582Ser) is associated with increased breast susceptibility but results remained controversial. Therefore, we performed the molecular evaluation of HIF-1α gene variation and determined its frequency and association with Breast Cancer susceptibility in Saudi Arabia.

Methods: This study was conducted on histologically confirmed Breast cancer patients and gender matched healthy women. HIF-1α C1772T (Pro582Ser) genotyping was done by Amplification refractory mutation system PCR method. The HIF-1α gene genotypes were correlated with different clinicopathological characteristics of breast cancer patients.

Results: A significant difference was observed in genotype distribution of HIF-1α gene variation C1772T (Pro582Ser) between breast cancer cases and gender matched healthy controls (P=0.010). Our findings showed that the HIF- 1α variant was associated with an increased risk of Breast cancer for HIF-1α CC vs CT genotype OR = 2.20, 95% CI = (1.28 -3.77), P = 0.004) in codominant inheritance model. The significant association was reported for HIF1A for genotypes CC vs (CT+ TT) OR = 1.98, 95% CI = (1.17-3.34), P = 0.010) in dominant inheritance model tested. In case of recessive inheritance model, a non-significant association of HIF-1 alpha gene variants was reported for (CC+ CT) vs TT) OR = 1.03, 95% CI = (0. 064-16.79), P = 0.97). During the allelic comparison, a non-significant association was reported between A vs C allele among Breast cancer patients. A significant association of HIF- 1α polymorphism was reported with stage as well as distant metastasis of the disease.

Conclusion: A significant difference was observed in genotype distribution of HIF-1α gene variation C1772T (Pro>Ser) between breast cancer cases and gene matched healthy controls (P=0.010). HIF-1α- CT heterozygosity and CC genotype increased the susceptibility .The HIF-1α polymorphism was reported to be significantly associated with the distant metastasis of Breast cancer. Further studies with larger data set and well-designed models are required to validate our findings.
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http://dx.doi.org/10.2174/1871530320666200910105214DOI Listing
November 2021

Correction to: Ectopic PD-L1 expression in JAK2 (V617F) myeloproliferative neoplasm patients is mediated via increased activation of STAT3 and STAT5.

Hum Cell 2020 Oct;33(4):1334

Department of Biochemistry, Maulana Azad Medical College and Associated Hospitals, Bahadur Shah Zafar Marg, New Delhi, 110002, India.

In the original publication, third author name was incorrectly published as "Ab Rashid Mir". The correct name should read as "Rashid Mir".
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http://dx.doi.org/10.1007/s13577-020-00394-yDOI Listing
October 2020
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