Publications by authors named "Khalil Mahmoodi"

12 Publications

  • Page 1 of 1

A preliminary study of the association between the gene promoter DNA methylation and coronary artery disease risk.

Mol Biol Res Commun 2018 Jun;7(2):59-65

Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.

Coronary artery disease (CAD) is a common health problem in Iranian population. ATP binding cassette transporter A1 (ABCA1) plays central role in the efflux of the cholesterol from peripheral tissues back to liver. Inactivation of ABCA1 by epigenetic change such as DNA methylation may contribute to the development of CAD. The present study investigated the association between promoter DNA methylation status of with the development and severity of CAD. Our study population consisted of 110 angiographically documented CAD patients and 110 controls. The severity of CAD was determined based on the number of stenotic vessels showing more than 50% stenosis. Promoter DNA methylation status of was determined by methylation specific PCR. Lipid profile was determined by routine colorimetric methods. Results showed that the frequency of DNA methylation was significantly higher in CAD group as compared with control group (16.36% 5.45%; P=0.015). Also, the methylation frequency of gene was significantly higher in older CAD patients as compared with younger CAD patients (P=0.038). No association was seen between plasma lipid concentration and the promoter DNA methylation status of (P>0.05). Also, the association between the severity of CAD and methylation of gene was not significant (P>0.05). In conclusion the current study indicated DNA methylation as a significant risk factor for development but not severity of CAD. Also, predisposition to the development of CAD by gene DNA methylation was independent of plasma lipid concentration.
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http://dx.doi.org/10.22099/mbrc.2018.28910.1312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6054780PMC
June 2018

The C-565T Polymorphism (rs2422493) of the ATP-binding Cassette Transporter A1 Gene Contributes to the Development and Severity of Coronary Artery Disease in an Iranian Population.

Oman Med J 2018 Jul;33(4):309-315

Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.

Objectives: ATP-binding cassette transporter A1 (ABCA1) plays a pivotal role in reverse cholesterol transport from peripheral tissues back to the liver. Abnormalities in ABCA1 function may lead to dyslipidemia and coronary artery disease (CAD). We investigated the role of C-565T (rs2422493) promoter polymorphism of ABCA1 gene in the development and severity of CAD in an Iranian subpopulation.

Methods: Our study population consisted of 110 angiographically-confirmed CAD patients and 110 matched controls. The severity of CAD was expressed based on the number of stenotic vessels. Genotyping of C-565T promoter polymorphism was performed using the polymerase chain reaction followed by restriction fragments length polymorphism analysis methods. Lipid profile was determined by routine colorimetric methods.

Results: The distribution of ABCA1 C-565T genotypes ( 0.035) and alleles ( 0.017) was significantly different between the CAD and control groups. In univariate analysis (with genotype CC as reference), the TT genotype was significantly associated with an increased risk of CAD (odds ratio = 3.83; 95% confidence interval: 1.29-11.30, 0.014), but the CT genotype was not ( 0.321). A multiple binary logistic regression analysis revealed that smoking, hypertension, triglyceride, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and ABCA1 C-565T dominant genotype were significant and independent risk factors for CAD development ( < 0.050). The ABCA1 C-565T polymorphism affected the severity of CAD in TT homozygote state ( 0.028). However, no significant correlation was seen between this common polymorphism and lipid profile in the study population ( > 0.050).  Our study indicated that ABCA1 C-565T polymorphism is a significant risk factor for development and severity of CAD in our population.
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http://dx.doi.org/10.5001/omj.2018.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6047175PMC
July 2018

The association between -94ATTG ins/del and 826C/T genetic variations and coronary artery disease risk.

Mol Biol Res Commun 2018 Mar;7(1):17-24

Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.

Coronary artery disease (CAD) is considered as a chronic inflammatory disease initiated from early childhood. Nuclear factor κB (NF κB) and κB1A (NF κB1A) are the key regulators of inflammatory responses. The -94ATTG ins/del and -826C/T polymorphisms may contribute to the development of CAD. The aim of the present study was to investigate the association of these polymorphisms with the risk of CAD. The study population included 120 patients with angiographically confirmed CAD and 100 matched controls. Genotyping of -94ATTG ins/del and -826C/T polymorphism was performed using PCR-RFLP method. Lipid level was determined by routine colorimetric methods. Statistical analysis was done by SPSS 16 software. Results indicated that the genotypic (P=0.041) and allelic (P=0.009) distribution of the NFKB1-94ATTG ins/del polymorphism was significantly different between the two groups. In the univariate analysis (ins/ins genotype as reference), the del/del genotype (OR=2.88, 95% CI=1.21-6.84, P=0.015) but not ins/del genotype (OR=1.48, 95% CI=0.83-2.64, P=0.191) was significantly associated with the increased risk of CAD. In the multiple binary logistic regression analysis, diabetes, hypertension, smoking, LDL-cholesterol, total cholesterol, HDL-cholesterol and -94ATTG del/del genotype were identified as significant and independent risk factors for CAD development. The distribution of genotypes and alleles of -826C/T polymorphism was not significantly different between the two groups. In conclusion the present study identified -94ATTG ins/del polymorphism but not -826C/T polymorphism as a significant and independent risk factor for development and severity of CAD.
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http://dx.doi.org/10.22099/mbrc.2018.28261.1302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5991530PMC
March 2018

Evaluation of the Role of -137G/C Single Nucleotide Polymorphism (rs187238) and Gene Expression Levels of the IL-18 in Patients with Coronary Artery Disease.

Oman Med J 2018 Mar;33(2):118-125

Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.

Objectives: Interleukin-18 (IL-18) is a proinflammatory and proatherogenic cytokine, and its genetic variations may contribute to the development of coronary artery disease (CAD). We sought to investigate the role of -137G/C polymorphism and gene expression levels of IL-18 in patients with CAD.

Methods: The study population included 100 patients with angiographically proven CAD and 100 matched controls. Total RNA and DNA were extracted from leukocytes using appropriate kits. The genotype of -137G/C polymorphism and gene expression level of IL-18 was determined using allele-specific polymerase chain reaction (PCR) and real-time (RT)-PCR assay, respectively.

Results: The genotypic and allelic distribution of IL-18 -137G/C polymorphism was not significantly different between the two groups ( > 0.050). Moreover, the -137G/C polymorphism did not increase the risk of CAD in dominant and recessive genetic models ( > 0.050). However, subgroup analysis of CAD patients revealed that the IL-18 -137G/C polymorphism was significantly associated with increased risk of CAD in hypertensive patients (odds ratio (OR) = 7.51; 95% confidence interval (CI): 1.24-25.17; 0.019) and smokers (OR = 4.90; 95% CI: 1.21-19.70; 0.031) but not in the diabetic subpopulation ( 0.261). The genotype distribution of IL-18 -137G/C genetic polymorphism was significantly different among patients with one, two, and three stenotic vessels ( < 0.050). The gene expression level of IL-18 was significantly higher in the CAD group than the control group ( < 0.001). Moreover, the carriers of CC genotype had significantly lower gene expression levels of IL-18 than carriers of GG genotype ( < 0.050).

Conclusions: The -137G/C polymorphism of IL-18 may be associated with the CAD risk in hypertensive and smoker subgroup of CAD patients. The -137G/C polymorphism seems to play an important role in determining the severity of CAD. Increased IL-18 gene expression level is a significant risk factor for the development of CAD. The CC genotype of -137G/C polymorphism is associated with lower IL-18 gene expression levels.
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http://dx.doi.org/10.5001/omj.2018.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5889842PMC
March 2018

Assessment of the role of plasma nitric oxide levels, T-786C genetic polymorphism, and gene expression levels of endothelial nitric oxide synthase in the development of coronary artery disease.

J Res Med Sci 2017 15;22:34. Epub 2017 Mar 15.

Department of Public Health, School of Public Health, Zanjan University of Medical Sciences, Zanjan, Iran.

Background: Reduced bioavailability of nitric oxide (NO) and the T-786C polymorphism of endothelial nitric oxide synthase (eNOS) gene have been reported as risk factors for the development of coronary artery disease (CAD) with conflicting results. We investigated the association of plasma NO levels, T-786C genetic polymorphism, and gene expression levels of eNOS with CAD risk in an Iranian subpopulation.

Materials And Methods: Studied population included 100 patients with angiographically verified CAD and 100 ethnically matched controls. Analysis of T-786C genetic polymorphism and gene expression levels of eNOS was conducted by polymerase chain reaction (PCR) restriction fragment length polymorphism and real-time reverse transcription-PCR methods, respectively. Plasma levels of NO were measured using Griess method.

Results: The CC genotype distribution (15% vs. 6%, = 0.011) and minor C allele frequency (36.5% vs. 21.5%, = 0.001) of eNOS T-786C polymorphism differed significantly between CAD patients and control. Furthermore, eNOS T-786C polymorphism was more common among smoker than nonsmoker CAD patients (27.7% vs. 7.8%, = 0.044). The association of the eNOS T-786C polymorphism with the severity of CAD (number of diseased vessel) was significant ( < 0.05). The gene expression levels of eNOS were significantly lower in the heterozygote (0.49 ± 0.1, = 0.023) and mutant homozygote (0.36 ± 0.09, = 0.011) genotypes than that of wild-type genotype ( < 0.05). In addition, NO levels were significantly lower in CAD patients compared with control subjects (42.62 ± 12.26 vs. 55.48 ± 16.57, = 0.002) and showed intergenotypic variation in the CAD patients.

Conclusion: Our study indicated that reduced NO levels and eNOS T-786C genetic polymorphism are significant risk factors for the development and severity of CAD in the Iranian population.
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http://dx.doi.org/10.4103/1735-1995.202144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5390540PMC
March 2017

Plasma concentration, genetic variation, and gene expression levels of matrix metalloproteinase 9 in Iranian patients with coronary artery disease.

J Res Med Sci 2017 27;22. Epub 2017 Jan 27.

Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.

Background: Matrix metalloproteinase 9 (MMP9) -1562C>T (rs3918242) polymorphism has been proposed as a risk factor for coronary artery disease (CAD) with conflicting results. The aim of the present study was to investigate the association of -1562C>T genetic polymorphism, gene expression and circulating levels of MMP9 with CAD risk in an Iranian subpopulation in in Zanjan City.

Materials And Methods: This was a retrospective case-control study we investigated retrospectively 100 patients with angiographically verified CAD and 100 matched controls. Genotyping of -1562C>T polymorphism was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Gene expression levels and circulating levels of MMP9 was determined by real-time reverse transcription-PCR and enzyme immunoassay method, respectively. Statistical analysis was done using Student's -test or Chi-square test by SPSS 16 software.

Results: The mean circulating levels of MMP9 were significantly higher in CAD Group than control group ( = 0.002). Mean plasma levels of MMP9 were also significantly higher in triple vessel stenosis patients than double vessel or single vessel stenosis patients ( < 0.001). Moreover, mean plasma levels and gene expression levels of MMP9 were significantly higher in T allele carrier than C allele carrier of MMP9 -1562C>T polymorphism ( = 0.002, = 0.01, respectively). However, genotype and allele frequencies of MMP9 -1562C>T polymorphism were similar between CAD patients and controls ( > 0.05). Additionally, the -1562C>T polymorphism of MMP9 gene didn't increase the risk of CAD in dominant ( = 0.537) or recessive ( = 0.249) genetic models.

Conclusion: Our study demonstrated that circulating levels of MMP9 but not -1562C>T polymorphism of MMP9 gene may be a risk factor for development and severity of CAD in an Iranian subpopulation in Zanjan.
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http://dx.doi.org/10.4103/1735-1995.199088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5361445PMC
January 2017

Association of Nitric Oxide Levels and Endothelial Nitric Oxide Synthase G894T Polymorphism with Coronary Artery Disease in the Iranian Population.

Vasc Specialist Int 2016 Sep 30;32(3):105-112. Epub 2016 Sep 30.

Department of Medical Laboratory Sciences, School of Paramedical Sciences, Zanjan University of Medical Sciences, Zanjan, Iran.

Purpose: The endothelial nitric oxide synthase (eNOS) G894T polymorphism has been reported to cause endothelial dysfunction and may have a role in the development of coronary artery disease (CAD). The aim of the present study was to investigate the association of eNOS G894T genetic polymorphism and plasma levels of nitric oxide (NO) with CAD risk in an Iranian population.

Materials And Methods: We studied 200 patients with angiographically documented CAD and 100 matched controls. Analysis of G894T genetic polymorphism of eNOS was performed by polymerase chain reaction-restriction fragment length polymorphism method. Plasma levels of NO were determined using Griess method. Biochemical analysis was conducted by routine colorimetric methods.

Results: Plasma levels of NO were significantly lower in CAD patients than control subjects (41.60±12.70 vs. 55.48±16.57, P=0.001). Also, the mean plasma levels of NO were significantly lower in T allele carriers of eNOS G894T polymorphism than G allele carriers (P<0.001). The genotype distribution and minor T allele frequency of eNOS G894T polymorphism significantly differed between CAD patients and control subjects (P<0.05). However, no significant association was found between the eNOS G894T polymorphism and the severity of CAD (number of diseased vessel) or the lipid profile of CAD patients (P>0.05).

Conclusion: Reduced plasma level of NO is associated with increased risk of CAD in our population. Moreover, eNOS G894T polymorphism is a significant risk factor for CAD development via reducing the plasma levels of NO. However, eNOS G894T polymorphism is not a contributing factor for the severity of CAD.
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http://dx.doi.org/10.5758/vsi.2016.32.3.105DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5045252PMC
September 2016

Evaluation of the protective effect of N-acetylcysteine on contrast media nephropathy.

J Renal Inj Prev 2015 1;4(4):109-12. Epub 2015 Sep 1.

Department of Internal Medicine, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran.

Introduction: Intravenous contrast agents can cause acute decline in kidney function, especially in patients with risk factors.

Objectives: In this study, we aimed to examine the ameliorative effect N-acetylcysteine (NAC) to reduce the incidence of contrast nephropathy.

Patients And Methods: This study was a prospective, randomized, double-blind clinical trial on 150 patients who underwent coronary angiography. The study was carried out on patients undergoing coronary angiography. Patients were randomly assigned into 2 groups of intervention group and control subjects. Intervention group took NAC 600 mg orally twice a day. It was administered one day before angiography and continued until the second day after angiography. Control subjects received saline only. Serum creatinine was measured before and three days after coronary angiography.

Results: There was no significant difference between intervention and control groups at baseline (P > 0.05). However, there was a significant decline in creatinine level among NAC patients (P = 0.001). Saline group had significantly higher proportion of nephropathy cases than NAC patients Conclusion: We found that the consumption of NAC is useful for contrast induced nephropathy (CIN) prevention.
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http://dx.doi.org/10.12861/jrip.2015.23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685979PMC
December 2015

The Efficacy of Hydration with Normal Saline Versus Hydration with Sodium Bicarbonate in the Prevention of Contrast-induced Nephropathy.

Heart Views 2014 Apr;15(2):33-6

Department of Madani Heart Centre, Tabriz University of Medical Science, Tabriz, Iran.

Background: Contrast-induced acute kidney injury [contrast-induced nephropathy (CIN)] is one of the major causes of hospital-acquired acute renal failure. Volume supplementation is the most effective strategy to prevent acute renal failure caused by contrast; but the effects of sodium bicarbonate regimens are unknown in CIN prevention. The aim of this survey is to compare the efficacy of hydration with normal saline versus hydration with sodium bicarbonate in the prevention of the CIN in patients undergoing coronary angiography.

Materials And Methods: In a clinical trial, 350 patients undergoing coronary interventions were randomized into two groups: One group received normal saline and another group received sodium bicarbonate before and after infusion of the contrast. Patients in both the groups had received N-acetylcysteine. CIN was defined as relative increase in serum creatinine equal to or more than 25% of baseline or increase to 0.5 mg/dl in 48 h after the injection of the contrast.

Results: CIN was seen in 46 patients (13.1%) after coronary interventions. Incidence of CIN in patients receiving normal saline (19.4%) was more than in patients receiving sodium bicarbonate (6.9%) (P = 0.001). Hemodialysis was needed only in one patient who received saline normal. Relative risk to induce CIN in both groups was as 2.8 and was in the range of 1.50-5.25 with confidence interval of 95% and P = 0.001. Thus, the probability of CIN was significantly more in the usage of normal saline.

Conclusion: This survey showed that hydration with sodium bicarbonate is superior to hydration with normal saline and has better protection effects.
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http://dx.doi.org/10.4103/1995-705X.137489DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4124663PMC
April 2014

A case-control study on the association of common variants of CAPN10 gene and the risk of type 2 diabetes in an Iranian population.

Clin Lab 2014 ;60(4):663-70

Background: Calpain-10 is a ubiquitously expressed protease that serves as an intracellular calcium-dependent cysteine protease and is regarded to be one of the candidate genes for type 2 diabetes mellitus (T2DM). We aimed to identify the association of the common variants of this gene and the risk of T2DM in the Kurdish ethnic group of Iran.

Methods: Study groups included 173 T2DM and 173 normoglycemic subjects. Genotyping was determined by PCR-RFLP. Genotypic and allelic frequencies were then evaluated. Data was analyzed using SPSS software.

Results: The allelic frequency of the A-allele of SNP-43 variant was significantly different (p = 0.01) between case and control groups (18% vs. 11%). The genotype frequencies for SNP-43 did not show any significant difference between case and control individuals. However, the dominant model of SNP-43 was found to be significantly associated with T2DM (OR = 1.75, 95% CI = 1.06 - 2.89, p < 0.029). The distribution and allele frequency of other SNPs (SNP-19 and -63) did not show any significant difference between the study groups. For SNP-43, fasting serum insulin (p = 0.043) and HOMA-IR (p = 0.026) were higher in the control subjects with the GA+AA genotype when compared with the GG genotype. Among the T2DM subjects, there was no significant difference in any of the clinical or biochemical parameters between the GG and GA+AA genotypes of SNP-43. Normoglycemic subjects carrying the 2R/3R+3R/3R genotypes of SNP-19 had significantly lower HDL-C (p = 0.034) as compared with those with the 2R/2R genotype. In T2DM subjects, no significant difference was found in any of the clinical or biochemical parameters between 2R/2R and 2R/3R+3R/3R genotypes. T2DM subjects carrying the CT+TT genotypes of SNP-63 variation had significantly higher LDL-C (p = 0.015) as compared with those with the CC genotype. In normoglycemic subjects, no significant difference was found in any of the clinical or biochemical parameters between CC and CT+TT genotypes.

Conclusions: Our findings revealed that there is an association between the SNP-43, but not SNP-19 and -63, and T2DM in the Kurdish ethnic group of West Iran.
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http://dx.doi.org/10.7754/clin.lab.2013.130630DOI Listing
May 2014

The impact of stepwise stent deployment on the angiographic and clinical outcome of coronary angioplasty in the setting of an acute myocardial infarction.

Saudi Med J 2011 Jun;32(6):571-8

Cardiovascular Research Department, Tabriz University of Medical Sciences, Daneshgah St., Tabriz, Iran.

Objective: To detect a reduction in the incidence of no-reflow, and a possible improvement in angiographic and clinical outcome after stepwise stenting in comparison with conventional method in the percutaneous coronary intervention (PCI) of patients with anterior ST elevation myocardial infarction.

Methods: Between March 2007 and December 2009, patients with anterior acute myocardial infarction (AMI) treated with streptokinase less than 6 hours from presentation who underwent early PCI were enrolled in this multicenter randomized clinical trial. The study was carried out in the Cardiology Departments of Valiasr Hospital of Zanjan, Imam Reza, and Shahid Madani Heart Hospitals, Tabriz, Iran.

Results: Four hundred and three patients were enrolled in this study. Patients were randomly divided into 2 groups: Group I (n=202) with stepwise stent deployment (SSD), and Group II (n=201) with routine conventional stent deployment (CSD). The patients' mean age was 57.7 +/- 10.7 years. After PCI, thrombolysis in myocardial infarction myocardial perfusion grade (TMPG) 0/1, suggestive of no-reflow was significantly higher in CSD group (p=0.0001). In hospital based, death occurred in 15 patients (7.5%) from CSD group while 4 (2%) from the SSD group (p=0.01). The TMPG was also significantly higher in SSD group (average 2.32 +/- 0.18) compared with CSD group, (average 1.66 +/- 0.24) (p=0.0001). Conventional stenting technique was an independent predictor of no-reflow in multivariate logistic regression analysis (hazard ratio - 1.43; 95% confidence interval: 1.15-1.73; p=0.01).

Conclusion: The SSD was associated with improved angiographic reperfusion indices and reduced mortality in early PCI for AMI.
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June 2011

Transpulmonary closing of left internal mammary artery to pulmonary artery fistula with polytetrafluoroethylene covered stent: a case report and review of literature.

Cardiol J 2009 ;16(5):469-72

Cardiovascular Research Department of Tabriz University of Medical Sciences, Tabriz, Iran.

Internal mammary artery (IMA) to pulmonary vasculature fistula is a rare condition that can be congenital or associated with coronary artery bypass grafting surgery (CABG), trauma, inflammation, or neoplasia. This complication may cause myocardial ischemia. CABG with an IMA conduit accounts for most iatrogenic cases, thus this problem may be encountered more in the future as the number of patients undergoing CABG and redo-CABG increases. The natural history of IMA-to-pulmonary artery (PA) fistulas is unknown and therefore optimal treatment remains controversial. We describe a case of left IMA-to-PA fistula treated with balloon expandable covered stent with a transpulmonary approach, and we review previously reported cases.
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November 2009