Dataset Information

Association between Coronary Artery Disease and rs10757278 and rs1333049 Polymorphisms in 9p21 Locus in Iran.

ABSTRACT: Background:Coronary arteries disease (CAD) has been recognized as one of the most common causes of death worldwide, with an estimated seven million deaths annually. Methods:Two hundred blood samples from Iranian CAD patients and normal healthy controls were collected. CAD and the 9p21 locus variants rs1333049 and rs10757278 were analyzed for potential associations. Results:No significant differences in rs10757278 and rs1333049 polymorphisms were found between patients and controls, but a significant relationship was found between rs10757278 and rs1333049 in CAD patients at the genotype level (p= 0.0323). At the haplotype level and on the basis of diplotype analysis, a significant relationship was found between patients and controls (OR= 5.16, p= 0.047, 95% CI: 1.02-26.0). In CAD patients, rs10757278 and rs1333049 were associated at locus 9p21. Conclusion:The inconsistency between the results of this and other studies on different CAD populations may be due to high population, different ethnicities, low prevalence of some alleles in populations, and interactions of different genes.

SUBMITTER: Yaghoubi Hariri F

PROVIDER: S-EPMC7424418 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Association between Coronary Artery Disease and rs10757278 and rs1333049 Polymorphisms in 9p21 Locus in Iran.

Yaghoubi Hariri Farbod F Salahshourifar Iman I Zare Karizi Shohreh S

Reports of biochemistry & molecular biology 20200401 1

<h4>Background</h4>Coronary arteries disease (CAD) has been recognized as one of the most common causes of death worldwide, with an estimated seven million deaths annually.<h4>Methods</h4>Two hundred blood samples from Iranian CAD patients and normal healthy controls were collected. CAD and the 9p21 locus variants <i>rs1333049</i> and <i>rs10757278</i> were analyzed for potential associations.<h4>Results</h4>No significant differences in <i>rs10757278</i> and <i>rs1333049</i> polymorphisms were ...[more]

PMID: 32821752

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Project description:ObjectiveCoronary artery disease (CAD) is a multi-factorial and heterogenic disease with atherosclerosis plaques formation in internal wall of coronary artery. Plaque formation results to limitation of the blood reaching to myocardium leading to appearance of some problems, such as ischemia, sudden thrombosis veins and myocardial infarction (MI). Several environmental and genetic factors are involved in prevalence and incident of CAD as follows: hypertension, high low density lipoprotein-cholesterol (LDL-C), age, diabetes mellitus, family history of early-onset heart disease and smoking. According to genome wide association studies (GWAS), five polymorphisms in the 9p21 locus seem to be associated with the CAD. We aimed to evaluate the remarkable association of two polymorphisms at 9p21 locus, rs1333049 and rs10757274, with CAD.Materials and methodsThis experimental study was conducted in Golestan, Aria Hospitals and Genetics Lab of Shahid Chamran University in the city of Ahvaz, Iran, in 2010- 2011. The collected blood samples belonging to 170 CAD patients (case group) and 100 healthy individuals (control group) were analyzed by tetra-primer amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) technique. The results were analyzed using software package used for statistical analysis (SPSS; SPSS Inc., USA) version 16. A value of p<0.05 and an odd ratio (OR) with 95% confidence intervals (CI) were considered significant.ResultsThe frequencies of CC, CG and GG genotypes for rs1333049 polymorphism in patients were 18.2, 65.3 and 16.5%, while in controls, the related values were 25, 67 and 8%, respectively. GG genotypes of rs1333049 polymorphism in CAD patients were more than control cases (OR: 0.354, 95%CI: 0.138-0.912, p=0.032). The frequencies of AA, AG and GG genotypes for rs10757274 in CAD patients were 8.2, 58.3 and 33.5%, while in controls, the related values were 35, 63 and 2%, respectively. GG Genotype in rs10757274 polymorphism in CAD patients was found more than control cases (OR: 0.014, 95% CI: 0.003 -0.065, p=0.0001).ConclusionThe rs1333049 polymorphism at 9p21 locus shows a weak association with CAD, whereas rs10757274 polymorphism reveals a significant association with CAD. These variants may help the identification of patients with increased risk for coronary artery disease.

Project description:ObjectiveTo study the interaction effects of rs10757278 polymorphisms at 9p21 locus and traditional risk factors on coronary heart disease (CHD) in Xinjiang, China.MethodsThis case-control study consecutively enrolled 310 unrelated consecutive CHD patients aged 18-70 years old. All study participants were recruited between January and December 2017 from The Heart Center of The First Affiliated Hospital of Xinjiang Medical University. CHD patients were confirmed by coronary angiography (≥50% diameter stenosis in at least one of the major coronary arteries) according to the American Heart Association criteria for the confirmation of CHD. Healthy subjects were randomly selected from the occupational population, who received physical examination in our hospital and matched to cases on the basis of age (±3 years) and sex, those without medical history of cardiovascular diseases, and 536 subjects were selected as the control group after medical history inquiry, physical examination, cardiac ultrasound, electrocardiogram, and other blood biochemical examinations in the hospital. The occupational stress was evaluated by an effort-reward imbalance questionnaire. An epidemiological survey was conducted to collect clinical data. Chi-squared test, analysis of variance, and binary logistic regression analysis were adopted.ResultsBoth the case and the control groups showed significant difference in smoking, drinking, physical activity, hypertension, diabetes mellitus, family history of CHD, and body mass index (BMI) (all P < 0.05); prevalence of CHD was not related to occupational stress. There was no significant difference in occupational stress level between the 2 groups (P > 0.05); Differences in rs10757278 genotype between the case group and the control groups were statistically significant; binary logistic regression analysis was used to evaluate the risk factors of CHD. After adjustment for age and sex, significant increased risk effects for CHD were found to be associated with smoking [odds ratio (OR) = 2.311; 95% confidence interval (CI): 1.04-2.499; P < 0.001], physical exercise (OR = 1.365; 95% CI: 1.137-1.639; P < 0.001), hypertension (OR = 4.627; 95% CI: 2.165-10.764; P < 0.001), family history of CHD (OR = 4.103; 95% CI: 3.169-6.892; P < 0.001), BMI (OR = 2.484; 95% CI: 2.036-3.03; P < 0.001), and GG genotype at rs10757278 (OR = 1.978; 95% CI: 1.413-2.769; P < 0.001); We noted that a significant interaction association between GG genotype at rs10757278 and CHD differs across categories of smoking, hypertension, family history of CHD, and BMI.ConclusionGG genotype at rs10757278 may be a risk factor for CHD. And there are interaction effects between GG genotype of rs10757278 in region 9p21 gene and traditional risk factors.

Project description:BackgroundCase-control Genome-Wide Association Studies (GWAS) have identified single nucleotide polymorphisms (SNPs) at the 9p21 locus as risk factors for coronary artery disease (CAD). The locus does not contain a clear candidate gene. Hence, the results of GWAS have raised an intense interest in delineating the basis for the observed association. We analyzed association of 4 SNPs at the 9p21 locus with the severity and progression of coronary atherosclerosis, as determined by serial quantitative coronary angiograms (QCA) in the well-characterized Lipoprotein Coronary Atherosclerosis Study (LCAS) population. The LCAS is a randomized placebo-control longitudinal follow-up study in patients with CAD conducted to test the effects of fluvastatin on progression or regression of coronary atherosclerosis.MethodsExtensive plasma lipid levels were measured at the baseline and 2 1/2 years after randomization. Likewise serial QCA was performed at the baseline and upon completion of the study. We genotyped the population for 4 SNPs, previously identified as the susceptibility SNPs for CAD in GWAS, using fluorogenic 5' nuclease assays. We reconstructed the haplotypes using Phase 2, analyzed SNP and haplotype effects using the Thesias software as well as by the conventional statistical methods.ResultsOnly Caucasians were included since they comprised 90% of the study population (332/371 with available DNA sample). The 4 SNPs at the 9p21 locus were in tight linkage disequilibrium, leading to 3 common haplotypes in the LCAS population. We found no significant association between quantitative indices of severity of coronary atherosclerosis, such as minimal lumen diameter and number of coronary lesions or occlusions and the 9p21 SNPs and haplotypes. Likewise, there was no association between quantitative indices of progression of coronary atherosclerosis and the SNPs or haplotypes. Similarly, we found no significant SNP or haplotype effect on severity and progression of coronary atherosclerosis.ConclusionWe conclude the 4 SNPs at the 9p21 locus analyzed in this study do not impart major effects on the severity or progression of coronary atherosclerosis. The effect size may be very modest or the observed association of the CAD with SNPs at the 9p21 locus in the case-control GWAS reflect involvement of vascular mechanisms not directly related to the severity or progression of coronary atherosclerosis.

Dataset Information

Association between Coronary Artery Disease and rs10757278 and rs1333049 Polymorphisms in 9p21 Locus in Iran.

Publications

Association between Coronary Artery Disease and rs10757278 and rs1333049 Polymorphisms in 9p21 Locus in Iran.

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