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GWAS implicated risk variants in different genes contribute additively to increase the risk of coronary artery disease (CAD) in the Pakistani subjects.

ABSTRACT: Coronary artery disease (CAD) remains the single most important cause of mortality worldwide. Many candidate and GWAS genetic variants have been identified in the recent years. In the current study, we selected six SNPs from various genes that have originally been identified in GWAS studies and examined the association of SNPs individually and as a genetic risk score (GRS) with CAD and blood lipid levels in the Pakistani subjects.Six hundred twenty-four (404 cases and 219 controls) subjects were genotyped for variants rs10757274 in CDKN2A gene, rs17465637 in MIA3 gene, rs7025486 in DAB2IP gene, rs17228212 in SMAD3 gene, rs981887 in MRAS gene and rs1746048 in CXCL12 gene, by TaqMan and KASPar allele discrimination techniques. Serum lipid parameters were measured using commercially available kits. Statistical analyses were done using SPSS version 22.Individually, the single SNPs were not associated with CAD (p?

SUBMITTER: Shahid SU

PROVIDER: S-EPMC5909255 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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GWAS implicated risk variants in different genes contribute additively to increase the risk of coronary artery disease (CAD) in the Pakistani subjects.

Shahid Saleem Ullah SU Shabana N A NA Rehman Abdul A Humphries Steve S

Lipids in health and disease 20180419 1

<h4>Background</h4>Coronary artery disease (CAD) remains the single most important cause of mortality worldwide. Many candidate and GWAS genetic variants have been identified in the recent years. In the current study, we selected six SNPs from various genes that have originally been identified in GWAS studies and examined the association of SNPs individually and as a genetic risk score (GRS) with CAD and blood lipid levels in the Pakistani subjects.<h4>Methods</h4>Six hundred twenty-four (404 ca ...[more]

PMID: 29673405

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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.

Project description:ObjectiveCoronary artery disease (CAD) risk stratification plays a fundamental role in the early detection and optimal management of CAD. The aim of our study is to investigate the use of coronary artery calcium scoring (CACS) as a tool for CAD risk stratification through evaluation of its correlation with the degree of coronary stenosis and its association with conventional cardiovascular risk factors in asymptomatic patients.DesignSingle-centre, retrospective, cross-sectional study.SettingThe study was conducted at a tertiary centre (Shifa International Hospital) in Islamabad, Pakistan, through review of medical records of patients who underwent coronary CT between the years 2016 and 2020.ParticipantsA total of 1014 patients were included in the study. The study population was analysed for presence of conventional risk factors (gender, age, diabetes, hypertension, body mass index, dyslipidaemia) and association with CACS (zero: n=534; minimal: 0 to ≤10, n=70; mild: >10 to ≤100, n=130; moderate: >100 to ≤400, n=118; and severe: >400, n=49). The association of CACS with the degree of coronary artery stenosis seen on CT scan (significant: ≥50% stenosis, n=216; non-significant: <50% stenosis, n=685) was also analysed.Outcome measuresThe main outcome was the association of coronary artery stenosis with CACS. The secondary outcome was the association of CACS with conventional CAD risk factors.ResultsA significant positive association was shown between CACS and coronary artery stenosis (zero vs minimal: OR 0.39, 95% CI 0.20 to 0.79, p=0.01; zero vs mild: OR 0.16, 95% CI 0.10 to 0.27, p<0.0001; zero vs moderate: OR 0.05, 95% CI 0.03 to 0.08, p<0.0001; zero vs severe: OR 0.02, 95% CI 0.01 to 0.050, p<0.0001). Age >45 (OR 1.03, 95% CI 1.01 to 1.05, p<0.0001), hypertension (OR 1.16, 95% CI 0.79 to 1.71, p=0.001) and diabetes (OR 1.33, 95% CI 0.88 to 1.99, p<0.0001) were associated with an increased risk of coronary artery stenosis. Moreover, plaques with higher calcium burden were found in the left anterior descending artery (mean CACS: 386.15±203.89), followed by right coronary (239.77±219.83) and left circumflex (175.56±153.54) arteries.ConclusionThe results indicate a strong positive association of CACS with coronary artery stenosis. CACS was also significantly associated with conventional CAD risk factors in this population.

Dataset Information

GWAS implicated risk variants in different genes contribute additively to increase the risk of coronary artery disease (CAD) in the Pakistani subjects.

Publications

GWAS implicated risk variants in different genes contribute additively to increase the risk of coronary artery disease (CAD) in the Pakistani subjects.

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