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Association between rs10757274 and rs2383206 SNPs as Genetic Risk Factors in Iranian Patients with Coronary Artery Disease.

ABSTRACT: Background: There are only a few reports concerning the genetic risk factors for coronary artery disease (CAD). However, 2 polymorphisms of rs10757274 and rs2383206 on chromosome 9p21.3 have been shown recently to be associated with CAD in certain populations. This is the 1st study to investigate their validity and association with CAD in a sample of the Iranian population. Methods: Genomic DNA was extracted from the peripheral blood of all participants, consisting of 111 cases with CAD and 100 normal controls with normal coronary angiographies. Genotyping of rs10757274 and rs2383206 was performed in the cases and controls using designed mismatch primers via the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: Statistical analysis presented a significant association between the rs10757274 GG (p value = 0.029, ?2 = 7.078) and rs2383206 GG (p value = 0.036, ?2 =6.658) genotypes and CAD among the cases as compared with the normal controls. Haplotype analysis of rs10757274 and rs2383206 polymorphisms showed 43% GG/GG haplotype with a significant association with CAD (p value = 0.014, ?² = 6.058). Conclusion: The results of this study provide an insight into the underlying molecular mechanism of CAD pathogenesis and pave the way for future functional studies on these variants.

SUBMITTER: Aleyasin SA

PROVIDER: S-EPMC5643868 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Association between rs10757274 and rs2383206 SNPs as Genetic Risk Factors in Iranian Patients with Coronary Artery Disease.

Aleyasin Seyed Ahmad SA Navidi Tayebe T Davoudi Saeed S

The journal of Tehran Heart Center 20170701 3

<b>Background:</b> There are only a few reports concerning the genetic risk factors for coronary artery disease (CAD). However, 2 polymorphisms of rs10757274 and rs2383206 on chromosome 9p21.3 have been shown recently to be associated with CAD in certain populations. This is the 1st study to investigate their validity and association with CAD in a sample of the Iranian population. <b>Methods:</b> Genomic DNA was extracted from the peripheral blood of all participants, consisting of 111 cases wit ...[more]

PMID: 29062378

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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:IntroductionThe present study aimed to investigate the association of the paraoxonase 1 (PON1) Q192R polymorphism with coronary artery disease (CAD) and cardiometabolic risk factors in Iranian patients suspected of CAD.MethodsThis cross-sectional study was conducted on 428 patients undergoing angiography. The data related to demographic information and physical activity were collected by valid and reliable questionnaires. The PON-1 genotypes were detected by the polymerase chain reaction-restriction fragment length polymorphism (RFLP-PCR) technique. The Gensini and SYNTAX score, anthropometric measurements, and biochemical and clinical parameters were measured by standard protocols.Results and discussionFindings indicated that the odds of obesity was significantly higher in people with the RR genotype compared to the QQ genotype carriers (OR: 2.95 CI: 1.25-6.93, P = 0.014) and also odds of low high-density lipoprotein cholesterol (HDL-C) was marginally higher (OR: 2.31 CI: 0.97-5.49, P = 0.056). There was no significant association between other CAD risk factors with PON1 Q192R polymorphism (P > 0.05). Further analysis showed a significant interaction between sex and 192QR (P = 0.019) and 192 RR (P = 0.007) genotypes on body mass index (BMI). More specifically, the risk of obesity in men carrying the RR genotype was 3.38 times (OR: 3.38 CI: 1.08-10.58, P = 0.036). Also, a significant joint effect of the RR genotype and sex on HDL-C was seen (P = 0.003). The stratification based on sex showed that the risk of low HDL-C is significantly higher in women carrying the RR genotype (OR: 6.18 CI: 1.21-31.46, P = 0.028). A marginal sex-genotype interaction was also found in the risk of elevated alanine aminotransferase (ALT) (P = 0.057). In summary, the findings showed that the risk of obesity and low HDL-C was higher in people carrying the RR genotype. On the other hand, a Q192R polymorphism-sex interaction was observed on the risk of obesity, elevated ALT, and low HDL-C.

Dataset Information

Association between rs10757274 and rs2383206 SNPs as Genetic Risk Factors in Iranian Patients with Coronary Artery Disease.

Publications

Association between rs10757274 and rs2383206 SNPs as Genetic Risk Factors in Iranian Patients with Coronary Artery Disease.

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