Publications by authors named "Shayan Ziaee"

24 Publications

  • Page 1 of 1

Predictive Inflammation-related microRNAs for Cardiovascular Events Following Early-Onset Coronary Artery Disease.

Arch Med Res 2021 01 28;52(1):69-75. Epub 2020 Nov 28.

Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Early-onset coronary artery disease (EOCAD) increases the risk of major cardiac adverse events (MACE) at the level of safety/effectiveness-related events. Since adverse events affect the quality of life of young patients with EOCAD, MACE prediction is of great importance for improving medical decision-making.

Aims Of The Study: We sought to determine whether the most important inflammation-related microRNAs in atherogenesis could predict MACE among patients with EOCAD.

Methods: This nested case-control study recruited 143 young patients (males ≤45 and females ≤55 years old), selected from a cohort of patients with premature coronary atherosclerosis at a median follow-up period of 64.1 months. Total RNAs were extracted from their peripheral blood mononuclear cells. The expression levels of 18 miRNAs, which are involved in inflammation and atherogenesis, were analyzed via quantitative reverse transcription PCR.

Results: A scoring model based on the upregulation of miR-146a_1 and miR-342_1, along with a history of myocardial infarction and the chronic usage of antithrombotic drugs, was able to predict MI/death at the level of safety-related events (higher vs lower risk scores: sHR: 4.61, 95% CI: 1.57-13.57, and p = 0.005). Another prediction model based on the downregulation of miR-145_1, age, and a history of unstable angina was also able to predict revascularization at the level of effectiveness-related events (higher vs lower risk scores: sHR: 2.90, 95% CI: 1.49-5.66, and p = 0.002).

Conclusions: Our results highlighted the role of miRNAs in adverse cardiac events and suggest that miR-146a_1, miR-342_1, and miR-145_1 may be useful biomarkers in predictive and preventive cardiology.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arcmed.2020.10.004DOI Listing
January 2021

Association of Preoperative Hemoglobin A1c with In-hospital Mortality Following Valvular Heart Surgery.

Braz J Cardiovasc Surg 2020 10 1;35(5):654-659. Epub 2020 Oct 1.

Tehran University of Medical Sciences Cardiovascular Diseases Research Institute Tehran Heart Center Tehran Iran Tehran Heart Center, Cardiovascular Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran.

Objective: To determine the association between the preoperative level of hemoglobin A1c (HbA1c) and in-hospital mortality in patients who underwent valvular heart surgery in our center in a retrospective cohort.

Methods: In this retrospective consecutive cohort study, patients with type 2 diabetes mellitus who were referred to our center for elective valvular surgery were enrolled and followed up. The endpoint of this study was in-hospital mortality. Based on the level of HbA1c, patients were dichotomized around a level of 7% into two groups: exposed patients with HbA1c ≥ 7% and unexposed patients with HbA1c < 7%. Then, the study variables were compared between the two groups.

Results: Two hundred twenty-four diabetic patients who were candidates for valvular surgery were enrolled; 106 patients (47.3%) had HbA1c < 7%, and 118 patients (52.6%) had HbA1c ≥ 7%. The duration of diabetes was higher in patients with HbA1c ≥ 7% (P=0.007). Thirteen (5.8%) patients died during hospital admission, of which nine patients were in the high HbA1c group. There was no significant difference between the groups regarding in-hospital mortality (P=0.899). Both the unadjusted and adjusted logistic regression models showed that HbA1c was not a predictor for in-hospital mortality (P=0.227 and P=0.388, respectively).

Conclusion: This study showed no association between preoperative HbA1c levels and in-hospital mortality in candidates for valvular heart surgery.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21470/1678-9741-2019-0320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598970PMC
October 2020

Prothrombin Gene G20210A Variant in Angiographically Documented Patients with Coronary Artery Stenosis.

J Tehran Heart Cent 2019 Oct;14(4):150-155

Department of Molecular Pathology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Studies on the association between the prothrombin G20210A variant and coronary artery disease (CAD) risk are inconclusive. This study aimed to investigate the possible association between the G20210A variant in the prothrombin gene and documented CAD and its severity. This study enrolled 1460 patients who were consecutively admitted for elective coronary angiography. Via the standard angiographic techniques, coronary angiographies were done and the presence and severity of CAD were determined through the clinical vessel score and the Gensini score. Prothrombin G20210A genotypes were identified using PCR-RFLP. This cross-sectional study was performed on 953 men and 507 women at a mean age of 58.21±10.33 years. The median and the interquartile range for the Gensini score were not statistically significantly different between the wild (GG) and mutant (AA+GA) genotypes (P=0.440). The association between the G20210A polymorphism and the severity of CAD with respect to the vessel score also showed no significant linear trend of higher numbers of diseased vessels (P= 0.765 for the Mantel-Haenszel test of linear trend) in the AA+GA genotype as compared with the GG genotype. Our data failed to confirm the hypothesis that the G20210A variant mutation may be a significant determinant of CAD risk or its severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7231676PMC
October 2019

The association between CYBA gene C242T variant and risk of metabolic syndrome.

Eur J Clin Invest 2020 Sep 29;50(9):e13275. Epub 2020 Jul 29.

Department of Pharmacology & Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.

Background: Both inflammation and oxidative stress may contribute to pathogenesis of metabolic syndrome (MetS). The C242T polymorphism (rs4673) in the CYBA gene, as the main components of NAD (P) H oxidase, causes inter-individual variability in the enzyme activity. We aimed to investigate the association between this polymorphism with MetS and its components.

Methods: Two hundred nine patients with MetS and 232 controls were included in this study. MetS was defined based on NCEP ATP-III A criteria with some modifications. The C242T polymorphism within CYBA gene was determined by using PCR-based restriction fragment length polymorphism (PCR-RFLP) method.

Results: After applying a multiple logistic regression model with adjusting for potential confounders of MetS including, age, sex, body mass index, hypertension, used medications, and diabetes mellitus, C242T polymorphism was found to be associated with the presence of MetS in men but not in the total population or in women. T allele as compared to C allele was associated with decreased odds of MetS in men (adjusted OR = 0.42, 95% CI = 0.24-0.74; P = .003), but not in women (adjusted OR = 1.03, 95% CI = 0.07-1.61; P = .890), or in the total population (adjusted OR = 0.72, 95% CI = 0.51-1.02; P = .063).

Conclusion: This study shows that T allele of C242T polymorphism in CYBA gene is protective against MetS in Iranian men but not in women. Further cohort studies with larger sample size in subgroups of men and women are required to confirm such association in other racial or ethnic group.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/eci.13275DOI Listing
September 2020

Association between polymorphisms in microRNA seed region and warfarin stable dose.

Postgrad Med J 2020 Dec 13;96(1142):737-741. Epub 2020 Jan 13.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Islamic Republic of Iran

Background: The optimal dose of anticoagulant warfarin varies among patients to achieve the target international normalised ratio. Although genetic variations related to warfarin pharmacokinetics and vitamin K cycle are important factors associated with warfarin dose requirements, these variations do not completely explain the large interindividual variability observed in the most populations, suggesting that additional factors may contribute to this variability. microRNAs have recently been introduced as regulators of drug function genes, and therefore, may be involved in drug responses. In this study, we aimed to evaluate the possible association between variants in the seed region of microRNAs, which target the genes involved in the action of warfarin and warfarin dose requirement.

Methods: 526 samples were collected from Iranian patients. Four selected polymorphisms in the seed region of microRNAs (rs2910164, rs66683138, rs12416605 and rs35770269 in miR-146a, miR-3622a, miR-938 and miR-449c, respectively) were genotyped by PCR-restriction fragment length polymorphism method.

Results: rs2910164 C/G in the seed region of miR-146a was associated with warfarin dose requirement (p<0.001); the patients with GG genotype had the higher mean dose of warfarin (40.6 mg/week, compared with 33.9 and 31.8 mg/week for GC and CC genotypes, respectively). The association of other polymorphisms with warfarin dose requirement was not statistically significant.

Conclusion: rs2910164 C/G in the seed region of miR-146a is associated with warfarin maintenance dose, likely by disrupting interaction between miR-146a and ATP-binding cassette subfamily B member 1 gene, ABCB1. Therefore, this polymorphism may possibly be a potential factor for assessment of warfarin dose requirements.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/postgradmedj-2019-137197DOI Listing
December 2020

Gene Polymorphism and Risk for Myocardial Infarction in Premature Coronary Disease.

Iran J Biotechnol 2019 Apr 20;17(2):e1921. Epub 2019 Apr 20.

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Contradictory results have been obtained regarding the role of integrin, beta 3 (ITGB3) gene polymorphisms in occurrence of myocardial infarction (MI).

Objectives: We aimed to assess the association between 1565C/T polymorphism of ITGB3 gene and increased risk for acute MI in patients with premature coronary artery disease (CAD).

Material And Methods: Our study included 1000 premature CAD patients that classified into two groups with history of MI (n = 461) and without of MI (n = 539). The polymorphism variants in 10% of samples were determined by PCR-RFLP technique and genotyping of the polymorphism in all subjects was conducted by High Resolution Melting method. Given the two conditions of patients residing in Tehran and also faced with their first episode of MI, 640 out of 1000 study samples that had been previously followed-up were assessed in a retrospective cohort phase regarding long-term major adverse cardiac events (MACE).

Results: There was no significant difference in the frequency of 1565C/T polymorphism between the MI and non-MI groups. The frequency of wild genotype was 69.2% and 72.2%, the frequency of homozygous genotype was 21.3% and 18.4%, and the frequency of mutant genotype was 9.5% and 9.5%, respectively (P = 0.505). No significant difference was also found in total-MACE free survival rate between the patients with different genotypes of 1565C/T polymorphism in both MI and non-MI group.

Conclusions: The carriage of the 1565C/T polymorphism of ITGB3 gene seems unlikely to be a significant risk factor for the development of MI in Iranian patients with premature CAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21859/ijb.1921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697842PMC
April 2019

Association between four microRNA binding site-related polymorphisms and the risk of warfarin-induced bleeding complications.

EXCLI J 2019 28;18:287-299. Epub 2019 May 28.

Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.

Bleeding is the most serious complication of warfarin anticoagulation therapy and is known to occur even at patients with therapeutic international normalized ratio (INR) range. Recently, it has been shown that microRNAs play a significant role in pharmacogenetics by regulating genes that are critical for drug function. Interaction between microRNAs and these target genes could be affected by single-nucleotide polymorphisms (SNPs) located in microRNA-binding sites. This study focused on 3'-untranslated region (3'-UTR) SNPs of the genes involved in the warfarin action and the occurrence of bleeding complications in an Iranian population receiving warfarin. A total of 526 patients under warfarin anticoagulation therapy with responding to the therapeutic dose and maintenance of the INR in the range of 2.0-3.5 in three consecutive blood tests were included in the study. Four selected 3'-UTR SNPs (rs12458, rs7294, rs1868774 and rs34669593 located in , , and genes, respectively) with the potential to disrupt/eliminate or enhance/create microRNA-binding site were genotyped using a simple PCR-based restriction fragment length polymorphism (PCR-RFLP) method. Patients with the rs12458 AT or TT genotypes of the gene had a lower risk of bleeding compared to patients with the AA genotype (adjusted OR: 0.478, 95% CI: 0.285-0.802, = 0.005, OR: 0.416, 95% CI: 0.192-0.902, = 0.026, respectively). 3'-UTR polymorphisms in other genes were not significantly associated with the risk of bleeding complications. In conclusion, the SNP rs12458A>T in the 3'UTR region of is associated with the incidence of warfarin-related bleeding at target range of INR, likely by altering microRNA binding and warfarin metabolism. Further genetics association studies are needed to validate these findings before they can be implemented in clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17179/excli2019-1352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6635724PMC
May 2019

Association between Serum Kalirin Levels and the gene rs9289231 Polymorphism in Early-Onset Coronary Artery Disease.

J Tehran Heart Cent 2018 Apr;13(2):58-64

Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.

Recently, rs9289231 genetic variations of kalirin (KALRN) have been introduced as potential genetic markers for coronary artery disease (CAD). However, the influence of KALRN single-nucleotide polymorphisms (SNPs) on serum kalirin levels has not been investigated in CAD patients so far. Thus, the present study aimed to survey whether SNP T>G (rs9289231) was associated with the risk of early-onset CAD and serum kalirin levels among the study subjects. The rs9289231 polymorphism of the KALRN was genotyped in 512 subjects (61.5% male, mean age=46.3±7.1 y), comprising 268 subjects with angiographically diagnosed CAD and 244 controls using an HRM assay. Also, the levels of serum kalirin were compared between 133 CAD subjects and 123 controls using a sandwich ELISA assay. The CAD subjects had more frequently GG genotypes than the controls. The odds ratio (OR) remained significant after adjustment for known CAD risk factors (OR=4.13, 95% CI: 2.48-9.10; P<0.001). A significant difference was also observed in that the G allele was more frequent among the CAD subjects. The G allele at the rs9289231 polymorphism was associated with a higher risk of CAD (OR=2.11, 95% CI: 1.27-2.59; P=0.001). The mean kalirin level of the CAD patients was higher than that of the controls (P=0.041). No significant correlation was seen in the different genotypes with serum kalirin levels. The KALRN rs9289231 T>G variant was considerably related with an increased risk of early-onset CAD. High kalirin levels were found in young CAD patients compared to the control subjects, with the levels not affected by the different genotypes of rs9289231.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6246431PMC
April 2018

Non-invasive diagnosis of early-onset coronary artery disease based on cell type-specific gene expression analyses.

Biomed Pharmacother 2018 Dec 29;108:1115-1122. Epub 2018 Sep 29.

Department of Genetics and Molecular Biology, Faculty of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran. Electronic address:

A non-invasive diagnostic method based on biomarkers related to endothelial and mononuclear cell dysfunction can provide opportunities for screening and early treatment of atherosclerosis. This study aimed to construct a risk scoring model based on clinical risk factors and molecular markers (lncRNA SENCR and CD markers) at single-cell level for early diagnosis of early-onset coronary artery disease (EOCAD). A single-cell expression analysis was performed on peripheral blood mononuclear cell subsets derived from 253 young individuals (Males ≤45 and Females ≤55 years old) in two training and validation sets using FISH-Flow assay. Concurrent quantifications of intracellular SENCR and surface/intracellular CD31, CD146, CD45 and CD14 in mononuclear cell fractions (Circulating endothelial cell, Monocyte and Lymphocyte) showed a significant reduction in intra-CEC SENCR, increased in intra-monocyte SENCR and also increased surface/intracellular CD146 and CD14 in patients with EOCAD as compared to the controls. Altered biomarkers were combined together as a risk scoring model. The ROC curve analysis on the combination model showed a high-performance in the distinction of our patients with EOCAD and healthy controls. A positive correlation between SENCR and CD14 in monocytes led us to find a binding site corresponding to SENCR and CD14 mRNA interaction. Our study suggested that combination of our molecular and clinical factors can be benefit to early diagnosis of EOCAD. CECs in peripheral blood as the novel approach could reflect molecular alteration in vascular endothelium. Bimodal variation in intracellular SENCR at the single-cell transcriptional level suggests that SENCR has cell-specific function(s) in its epigenetic gene regulation mechanisms.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biopha.2018.09.134DOI Listing
December 2018

Association between FTO gene polymorphisms and type 2 diabetes mellitus, serum levels of apelin and androgen hormones among Iranian obese women.

Gene 2018 Jan 31;641:361-366. Epub 2017 Oct 31.

Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran; Department of Clinical Biochemistry and Laboratory Sciences, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran. Electronic address:

Background And Aims: Recent studies show that FTO single nucleotide polymorphisms (SNPs) are associated with obesity and type 2 diabetes mellitus (T2DM). On the other hand, many animal models and clinical studies have demonstrated that apelin, an adipocytokine, is related to the obesity and T2DM. Additionally, obese women are at risk of Hyperandrogenemia. So, the aim of this study was to investigate the relationship between FTO variants (rs763967273, rs759031579, rs141115189, rs9926289, rs76804286 and rs9939609) with T2DM, serum apelin and androgenic hormones in Iranian obese women.

Subjects And Methods: 197 obese women (123 women with T2DM and 74 women as healthy control) were participated in this study. Anthropometrical and biochemical characteristics were measured. Serum apelin and androgen hormones levels were determined in 66 subjects consisting of 33 cases and 33 controls. PCR were carried out and subsequently, the PCR production was genotyped by Sanger sequencing assay.

Results: Our observations showed that all SNPs are related to T2DM. The rs9926289 FTO variant had a strong association with serum apelin and dehydroepiandrosterone-sulfate levels (P=0.04 and P=0.03, respectively) among SNPs. In addition, apelin and androgenic hormones were correlated with T2DM. Two polymorphisms including rs9939609 and rs9926289 had a strong Linkage disequilibrium (r=1).

Conclusion: FTO variants not only were associated with T2DM, but also some variants had a strong association with apelin and androgenic hormones profile.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.gene.2017.10.082DOI Listing
January 2018

Association between the Hepatic Lipase Promoter Region Polymorphism (-514 C/T) and the Presence and Severity of Premature Coronary Artery Disease.

J Tehran Heart Cent 2017 Jul;12(3):119-127

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Hepatic lipase (HL) plays a crucial role in lipid metabolism, but there is debate about whether HL acts in a more pro- or more anti-atherogenic fashion. We aimed to examine the relationship between the -514 C/T polymorphism within the HL gene (LIPC) and the risk of angiographically determined premature coronary artery disease (CAD). Four hundred seventy-one patients with newly diagnosed angiographically documented (≥ 50% luminal stenosis of any coronary vessel) premature CAD were compared to 503 controls (subjects with no luminal stenosis in coronary arteries). A real-time polymerase chain reaction and high-resolution melting analysis was used to distinguish between the genotypes. There was no significant difference in the distribution of -514 C/T genotypes between the 2 groups in the whole population or in the men, but the examined polymorphism was found to be associated with the presence of CAD in the women (p value = 0.029). After the application of a multiple logistic regression model, the minor T allele of the LIPC gene was not found to be independently associated with the presence of CAD either in the total population (adjusted OR = 0.97, 95% CI = 0.75-1.25; p value = 0.807) or in the women (adjusted OR = 0.91, 95% CI = 0.59-1.40; p value = 0.650) and in the men (adjusted OR = 1.15, 95% CI = 0.81-1.64; p value = 0.437) separately. Our findings suggest that there is no relationship between the LIPC -514 C/T and the risk of premature CAD or its severity in patients undergoing coronary angiography.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5643869PMC
July 2017

C1019T Polymorphism in the Connexin 37 Gene and Myocardial Infarction Risk in Premature Coronary Artery Disease.

J Tehran Heart Cent 2017 Apr;12(2):72-81

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

The C1019T polymorphism of the connexin-37 (GJA4) gene is a single-nucleotide polymorphisms involved in atherosclerotic plaque rupture and atherosclerosis predisposition. We examined the association between the C1019T polymorphism of the GJA4 gene and the occurrence of myocardial infarction (MI) in patients with premature coronary artery disease (CAD). Our study recruited 1000 patients with the final diagnosis of premature CAD and classified them into 2 groups: with a history of MI (n = 461) and without it (n = 539). The polymorphism variants were determined via the PCR-RFLP, and then genotyping was conducted through the high-resolution melting method. From a total of 1000 patients, 554 patients, who had been previously followed-up with a median follow-up time of 45.74 months vis-à-vis long-term major adverse cardiac events, were enrolled in this retrospective cohort phase. The frequencies of the wild, heterozygous, and mutant genotypes of the C1019T polymorphism were 54.0%, 40.6%, and 5.4% in the MI group and 49.2%, 43.2%, and 7.6% in the non-MI group (p value = 0.187). After adjustment for the baseline covariates, no difference was found between the MI and non-MI groups apropos the frequency of the heterozygous genotype (p value = 0.625) and the mutant genotype (p value = 0.452). Regarding the level of human connexin-37, the serum level of this marker was not different between the MI and non-MI groups. The C1019T polymorphism of the GJA4 gene may not be useful for predicting the occurrence of MI in patients with premature CAD. The presence of this polymorphism in such patients may also have a low value for predicting long-term CAD complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5558058PMC
April 2017

Association of R279Q and C1562T polymorphisms of matrix metalloproteinase 9 gene and increased risk for myocardial infarction in patients with premature coronary artery disease.

J Clin Lab Anal 2018 Jan 28;32(1). Epub 2017 Apr 28.

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: A number of matrix metalloproteinase (MMP) gene polymorphisms has been identified which may be probably related to premature myocardial infarction (MI).

Objective: We assessed the relationship between the two polymorphisms of the MMP9 gene including R279Q and C1562T and occurrence of premature MI.

Methods: The study has two phases including a case-control study as the first phase and cohort study as the second phase. Initially, 1000 patients with premature coronary artery disease were classified into MI and non-MI groups. Genotyping of the polymorphism was conducted by PCRRFLP and high-resolution melting techniques. Given the two conditions of patients residing in Tehran and faced with their first episode of MI, 640 of 1000 study samples previously followed up with a median follow-up time of 45.74 months were assessed in a retrospective cohort phase regarding long-term major adverse cardiac events (MACE).

Results: The prevalence of wild, heterozygous, and mutant genotypes of R279Q polymorphism in MI group was 14.5%, 57.3%, and 28.2% and in non-MI group was 36.9%, 38.4%, and 24.7%, respectively, with a considerable difference (P<.001). There was a significant difference in the prevalence of wild, heterozygous, and mutant genotypes of C1562T polymorphisms in MI group (12.4%, 41.2%, and 46.4%, respectively) and in non-MI group (46.8%, 38.6%, and 14.7%, respectively; P<.001). No difference was found in total MACE-free survival rate between genotypes of R279Q and C1562T polymorphisms.

Conclusion: C1562T and R279Q polymorphisms are associated with the susceptibility to premature MI, but cannot predict long-term cardiac events in these patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.22218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817094PMC
January 2018

The impact of vascular endothelial growth factor +405 C/G polymorphism on long-term outcome and severity of coronary artery disease.

J Clin Lab Anal 2017 Jul 5;31(4). Epub 2016 Oct 5.

Department of Biostatistics, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: The association between genetic variations of vascular endothelial growth factor (VEGF) gene and the risk for atherosclerosis has been hypothesized. We aimed to assess the relationship between rs2010963 (+405 C/G) polymorphism and presence, severity, and outcome of coronary artery disease (CAD) in an Iranian cohort.

Methods: Genotyping of VEGF rs2010963 polymorphism was performed on 520 individuals, comprising 347 patients with documented coronary artery disease based on angiography report and 173 individuals with normal coronary arteries, using the TaqMan real-time PCR method. In final, 484 subjects were followed up over a 5-year period for cardiovascular-related outcomes.

Results: C allele of VEGF rs2010963 polymorphism was related to increase risk for CAD and also slightly to 5-year cardiovascular mortality. The 5-year survival in C and G allele subgroups were 92.3% and 94.3% in CAD group and 95.7% and 98.0% in non-CAD group, respectively.

Conclusions: Vascular endothelial growth factor rs2010963 polymorphism may be associated with the presence of CAD and its long-term survival, but not with its severity. To the best of our knowledge, this is the first report of genetic association between rs2010963 SNP and CAD-related death. It can be thus suggested that rs2010963 VEGF gene can be considered as a genetic risk predictor for CAD and its outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jcla.22066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6816936PMC
July 2017

Gene polymorphisms and the risk of warfarin-induced bleeding complications at therapeutic international normalized ratio (INR).

Toxicol Appl Pharmacol 2016 10 28;309:37-43. Epub 2016 Aug 28.

Department of Pathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, P.O. Box 1411713138, Tehran, Iran. Electronic address:

Background: Bleeding episodes commonly occur in patients on warfarin treatment even in those within therapeutic range of international normalized ratio (INR). The objective of this study was to investigate the effects of the 8 examined polymorphisms on the risk of bleeding complications in a sample of Iranian patients.

Methods: A total of 552 warfarin treated patients who maintained on a target INR level of 2.0-3.5 for at least three consecutive intervals were enrolled from those attended our anticoagulation clinics. Ninety-two bleeding events were observed in 87 patients. The presences of the examined polymorphisms were analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP).

Results: Patients with the T allele in NQO1*2 (CT or TT genotypes) had a higher risk of bleeding than patients with the CC genotype (adjusted OR: 2.25, 95% CI: 1.37 to 3.70, P=0.001). Those who were carriers of CYP2C9 one-variant haplotypes (*1/*2 or *1/*3) were also found to be associated with the higher risk of bleeding events. Compared to reference group (*1/*1), the odds of bleeding increased for carriers of one variant allele (*1/*2 or *1/*3) (adjusted OR: 1.75, 95% CI: 1.03 to 2.97, P=0.039). Variant VKORC1, Factor VII, and EPHX1 genotypes were not significantly associated with the risk of bleeding events.

Conclusion: The SNP C609T within NQO1 and haplotypes of CYP2C9 (1*2 or 1*3) are independently associated to bleeding complications of warfarin at normal INR. Further studies are required to confirm such associations in diverse racial and ethnic populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.taap.2016.08.026DOI Listing
October 2016

Association of KALRN, ADIPOQ, and FTO gene polymorphism in type 2 diabetic patients with coronary artery disease: possible predisposing markers.

Coron Artery Dis 2016 Sep;27(6):490-6

aDepartment of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz Departments of bMolecular Pathology cPathology and Laboratory Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Objectives: Recently, several genes have been introduced as potential genetic markers for diabetes mellitus and coronary artery diseases (CAD).

Methods: In this case-control study, the associations of rs2241766 T/G of ADIPOQ, rs9289231 T/G of KALRN, and rs9939609 A/T of FTO polymorphisms with genetic susceptibility to CAD in type 2 diabetic (T2D) patients were investigated. A total of 224 T2D patients undergoing coronary angiography were randomly recruited into the study. Of the total diabetic patients, 152 were also diagnosed with CAD, whereas the rest were control participants. Genotyping of single-nucleotide polymorphisms was performed by high-resolution melting analysis.

Results: Genotype analysis showed that the minor allele (G) frequency of rs2241766 ADIPOQ was statistically significant in the CAD group compared with the control group [odds ratio (OR), 2.779; 95% confidence interval (CI), 1.403-5.504; P=0.003]. Also, it was found that the minor allele (G) frequency of rs9289231 KALRN was significantly associated with the risk of CAD (OR, 2.098; 95% CI, 1.096-4.017; P=0.025). In addition, no significant association was observed between the minor allele (A) of the FTO rs9939609 polymorphism and CAD (OR, 1.088; 95% CI, 0.578-2.015; P=0.788). It is speculated that the GG genotype and the G allele of the rs9289231 polymorphism of KALRN and the rs224766 polymorphism of ADIPOQ genes may be considered genetic risk factors for CAD in T2D patients and genetic variations of these genes may play a major role in the process of these disorders.

Conclusion: Our case-control study in the Iranian population suggested a possible association between the mentioned single-nucleotide polymorphisms and CAD in T2D patients. However, further replication studies and comprehensive meta-analyses are required.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCA.0000000000000386DOI Listing
September 2016

Cholesteryl ester transfer protein gene polymorphism (I405V) and premature coronary artery disease in an Iranian population.

Bosn J Basic Med Sci 2016 Jan 14;16(2):114-20. Epub 2016 Jan 14.

Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

The effect of human cholesteryl ester transfer protein (CETP) expression on atherogenesis is still under debate. The rs5882 (I405V) polymorphism affect CETP function. We aimed to examine the relationship between the rs5882 polymorphism and the risk of angiographically determined coronary artery disease (CAD). To define premature CAD (PCAD), an age cutoff of 55 years for women and 45 years for men was used. An age- and sex-matched case-control study was conducted in 560 patients with newly diagnosed angiographically documented PCAD (≥50% luminal stenosis of any coronary vessel) and an equal number of control patients with normal coronary arteries (no luminal stenosis at coronary arteries). The severity of CAD was determined by vessel score and Gensini score. A real-time polymerase chain reaction (PCR) and high resolution melting analysis were used to distinguish between genotypes. The I405V genotype distributions were not statistically different in CAD and non-CAD groups in univariate and multivariable-adjusted logistic regression analyzes. The median and inter-quartile range for Gensini score was not significantly different among the AA (43, 24 to 73), AG (40, 20 to 66), and GG (45, 25 to 72) genotypes (p = 0.097). Furthermore, the distribution of vessel score did not statistically differ between these genotypes (p = 0.691). Our results suggest that there is no significant association between CETP I405V polymorphism and the risk of PCAD presence and severity. Larger prospective studies are needed to investigate such associations in different populations.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.17305/bjbms.2016.942DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4852992PMC
January 2016

The rs5888 single nucleotide polymorphism in scavenger receptor class B type 1 (SCARB1) gene and the risk of premature coronary artery disease: a case-control study.

Lipids Health Dis 2016 Jan 12;15. Epub 2016 Jan 12.

Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Several single nucleotide polymorphisms (SNPs) in lipid transport genes have been shown to be associated with premature coronary artery disease (PCAD). The scavenger receptor BI (SCARB1) is a key component of the reverse cholesterol transport and lipid metabolism. We aimed to examine the relationship between the rs5888 SNP within SCARB1and the risk of angiographically determined PCAD.

Methods: We used an age cut-off of 55 years for women and 45 years for men to define PCAD. Five-hundred and five patients with newly diagnosed angiographically documented PCAD (≥ 50 % luminal stenosis of any coronary vessel) as case group compared with 546 controls (subjects with no luminal stenosis at coronary arteries). The severity of CAD was determined by vessel score as well as Gensini score. A real-time polymerase chain reaction (PCR) and High Resolution Melting (HRM) analysis was used to distinguish between genotypes.

Results: T allele as compared to C allele was associated with increased odds of PCAD in total population (adjusted OR = 1.3, 95 % CI = 1.0 to 1.5; p = 0.020), and in women (adjusted OR = 1.3, 95 % CI = 1.0 to 1.8; p = 0.037), but not in men (adjusted OR = 1.2, 95 % CI = 0.9 to 1.5; p = 0.311). There was also no significant association between the examined polymorphism and the severity of CAD in whole or in men or women subgroups.

Conclusions: Our findings suggest that the SNP (rs5888) within SCARB1 is independently associated with PCAD in a sex-dependent manner.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12944-016-0176-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4709878PMC
January 2016

NQO1 C609T Polymorphism is Associated with Coronary Artery Disease in a Gender-Dependent Manner.

Cardiovasc Toxicol 2017 01;17(1):35-41

Department of Pharmacology and Toxicology, School of Pharmacy, Kerman University of Medical Sciences, Kerman, P.O. Box 7616911319, Iran.

Findings on the association of NQO1 C609T polymorphism in the NQO1 gene and cardiovascular disease susceptibility are controversial. The objective of the current study was to examine the relationship between this polymorphism and the presence and severity of angiographically determined coronary artery disease (CAD). One-hundred and forty-five patients with newly diagnosed angiographically documented CAD (≥50 % luminal stenosis of any coronary vessel) as case group were compared to 139 controls (subjects with no luminal stenosis at coronary arteries). The presence of C609T polymorphism was analyzed using polymerase chain reaction-based restriction fragment length polymorphism. Among total population, those with combined CT/TT (T allele carrier) genotype showed a trend toward lower odds of CAD compared to those with CC (wild type) genotype, but it did not reach a statistically significant level (p = 0.061). When data were analyzed separately for men or women, CT + TT group as compared to CC genotype was associated with decreased odds of CAD in women (adjusted OR 0.4, 95 % CI 0.2-0.9; p = 0.043), but not in men (adjusted OR 0.8, 95 % CI 0.3-1.9; p = 0.612). The C609T polymorphism within NQO1 is independently associated with CAD in women, but no association was observed in whole study population or in men.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12012-015-9353-8DOI Listing
January 2017

The Kalirin Gene rs9289231 Polymorphism as a Novel Predisposing Marker for Coronary Artery Disease.

Lab Med 2014 ;45(4):302-8

Department of Molecular Pathology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Atherosclerosis is the leading cause of death and disability worldwide. Genetic variations play a major role in the process of atherosclerosis. Recently, rs9289231 genetic variations of the Kalirin gene (KALRN) on chromosome 3q21.2 have been introduced as potential genetic markers for coronary artery disease (CAD).

Objective: In this case-control study, we investigated the association between genetic susceptibility to CAD and rs9289231 G/T polymorphism, located on the KALRN gene, in an Iranian population.

Methods: Our cohort consisted of 1486 individuals undergoing coronary angiography. Of these, we considered the 1007 patients with CAD to be case individuals and the 479 individuals with normal coronary conditions to be control individuals. We performed single-nucleotide polymorphism (SNP) genotyping via the high resolution melting (HRM) technique.

Results: Our data showed that the minor allele (G) frequency of rs9289231 SNP was higher in our CAD group than that in our control group (odds ratio, 1:37; confidence interval, 1.07-1.74; P = .01). The results of our data analysis highlighted a genetic association between rs9289231 polymorphism and severity and development of CAD.

Conclusions: We consider the GG genotype and the G allele of rs9289231 polymorphism of KALRN to be genetic risk factors for CAD in an Iranian population, especially in early-stage atherosclerotic vascular disease.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1309/LMLS813ZDPHRFLUUDOI Listing
May 2016

Association between the atrial natriuretic peptide rs5065 gene polymorphism and the presence and severity of coronary artery disease in an Iranian population.

Coron Artery Dis 2014 May;25(3):242-6

Department of Pathology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Objective: The atrial natriuretic peptide (ANP) gene expression and some of its related single-nucleotide polymorphisms have been well established as a characterized biomarker of cardiovascular diseases. In the present study, we aimed to evaluate the potential association between one of the introduced ANP gene polymorphisms of 2238 T/C (rs5065) with coronary artery disease (CAD) in an Iranian population.

Basic Methods: A total of 573 patients with CAD according to angiography reports and 293 controls without any evidence of CAD were enrolled. Allelic discrimination of the single-nucleotide polymorphism rs5065 in both groups was performed using a High Resolution Melt technique in real-time PCR analysis.

Main Results: With respect to the prevalence of different genotypes of rs5065 polymorphism, the frequency of the T allele in the CAD group was significantly lower in CAD than that in the non-CAD group (59.7 vs. 65.1%, P=0.032). A significant inverse association was also found between the frequency of T allele and severity of CAD assessed by the Gensini score; the average of this score in T-allele carriers was 38.6±41.6 and that in C-allele carriers was 57.7±46.3 (P≤0.0001). Using multivariable linear regression modeling with the presence of baseline variables, the presence of the rs5065 ANP T allele could predict decreased severity of CAD assessed by the Gensini score in our population.

Principal Conclusion: The presence of the rs5065 ANP polymorphism is potentially associated with a reduced risk of CAD as well as with reduced severity of CAD independent of the general risk factors of CAD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MCA.0000000000000075DOI Listing
May 2014

Association between R353Q polymorphism for coagulative factor VII and severity of coronary artery disease in Iranian population.

Cardiol J 2013 ;20(5):533-8

Pathology, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: Recent research has supported the central role of coagulative factors in advancing atherosclerosis and causing coronary artery disease (CAD). The present study, for the first time, aimed to clarify the relationship between R353Q polymorphism for factor VII and the occurrence and severity of CAD in a large sample of Iranian population.

Methods: Nine hundred and nineteen consecutive patients with suspected CAD, who candidated for coronary angiography in the Tehran Heart Center between January 2006 and March 2007, were examined. The number of diseased coronary vessels was determined, and the severity of CAD was assessed by the Gensini score. Genotyping was done via the PCR-RFLP method.

Results: The frequency of Q and R alleles was 74.1% and 25.9% in the patients with CADand 75.2% and 24.8% in those without CAD, with an insignificant difference (p = 0.625). The frequency of Q allele in the patients with single-vessel, two-vessel, and three-vessel diseases was 72.8%, 71.5%, and 76.4%, respectively; the difference was also insignificant (p = 0.379). No relationship was observed between the distribution of the genotypes and the number of the involved coronary vessels. The average of the Gensini score was 43.39 ± 46.18 in the patients with QQ genotype, 38.87 ± 42.89 in those with QR genotype, and 55.61 ± 53.80 in the ones with RR genotype, with the difference not constituting any statistical significance (p = 0.084).

Conclusions: The results suggest no association between R353Q polymorphism for factor VII and the presence or progression of CAD in the Iranian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5603/CJ.2013.0139DOI Listing
August 2014

The association between Factor V Leiden with the presence and severity of coronary artery disease.

Clin Biochem 2014 Apr 17;47(6):356-60. Epub 2013 Dec 17.

Department of Cardiac Research, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran. Electronic address:

Objectives: The presence of Factor V Leiden (FVL) is proposed to be associated with a higher risk for arterial thrombosis. The aim of this study was to examine a relationship between FVL with the presence and severity of angiographically determined coronary artery disease (CAD).

Design And Methods: In this case-control study, 1083 patients having angiographic evidence of atherosclerosis with ≥50% luminal stenosis in their epicardial coronary tree were compared with patients with no luminal stenosis (n=320) or with luminal stenosis <50% (n=191) at coronary angiography as reference group. The severity of CAD was determined by vessel score and also a semi-quantitative scoring system (Gensini score). The presence of Factor V polymorphisms was analyzed using polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP).

Results: FVL was found to be independently associated with the occurrence of CAD (p=0.020). As compared to wild genotype, heterozygote or homozygote mutant genotypes were more likely associated with a trend towards more severe CAD (adjusted OR=1.85, 95% CI=1.26 to 2.72; p=0.002, and adjusted OR=3.70, 95% CI=1.71 to 8.00; p=0.001; respectively). In addition, the median and inter-quartile range for Gensini score were significantly different among the GG (27.8, 3 to 66.5), GA (53.5, 10 to 104.1), and AA (92.8, 48.1 to 125.9) genotypes (p<0.001).

Conclusions: Our results confirmed the hypothesis that FVL mutation is a significant determinant of CAD risk. Furthermore, we observed that FVL is independently associated with increasing CAD severity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinbiochem.2013.12.006DOI Listing
April 2014

Angiotensin- converting enzyme insertion/deletion polymorphism and its association with coronary artery disease in an Iranian population.

J Tehran Heart Cent 2013 Apr 28;8(2):89-94. Epub 2013 Apr 28.

Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran.

Background: The study of the association between genotype and phenotype is of great importance for the prediction of many diseases and pathophysiological conditions. The relationship between angiotensin-converting enzyme (ACE) gene insertion/ deletion (I/D) polymorphism and pathological processes such as coronary artery disease (CAD) has been investigated previously with discordant results. This study was designed to determine the association between ACE gene I/D polymorphism and CAD in an Iranian population.

Methods: A total of 1050 individuals who were referred to Tehran Heart Center for coronary angiography were recruited. Six hundred seventy-six CAD-positive patients (documented by coronary angiography and Gensini scores higher than 6) and 374 CAD-negative patients were evaluated for ACE gene I/D polymorphism via the Polymerase Chain Reaction Amplification method. The patients' age, sex, smoking status and its duration as well as familial history of CAD, hypertension, and diabetes mellitus were recorded.

Results: Five hundred four (74.6%) of the CAD-positive patients were male, and the mean age of this group was 60 (60 ± 10). In the CAD-negative individuals, the mean age was 56 (56 ± 10) and 196 of them were male (52.4%). After the analysis of all the groups and gender subgroups, neither genotype nor allele frequency was significantly different between the CAD-positive and CAD-negative groups (p values for genotypes and allele frequencies were 0.494 and 0.397, respectively).

Conclusion: ACE gene I/D polymorphism was not associated with an increased risk of CAD in an Iranian population.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3740114PMC
April 2013