Abstract
Recent genome-wide association studies identified single nucleotide polymorphisms (SNPs) on the chromosome 9p21.3 conferring the risk for CAD (coronary artery disease) in individuals of Caucasian ancestry. We performed a genetic association study to investigate the effect of 12 candidate SNPs within 9p21.3 locus on the risk of CAD in the Saudi population of the Eastern Province of Saudi Arabia. A total of 250 Saudi CAD patients who had experienced an myocardial infarction (MI) and 252 Saudi age-matched healthy controls were genotyped using TaqMan assay. Controls with evidenced lack of CAD provided 90% of statistical power at the type I error rate of 0.05. Five percent of the results were rechecked for quality control using Sanger sequencing, the results of which concurred with the TaqMan genotyping results. Association analysis of 12 SNPs indicated a significant difference in the genotype distribution for four SNPs between cases and controls (rs564398 p = 0.0315, χ2 = 4.6, odds ratio (OD) = 1.5; rs4977574 p = 0.0336, χ2 = 4.5, OD = 1.4; rs2891168 p = 1.85 × 10 − 10, χ2 = 40.6, OD = 2.1 and rs1333042 p = 5.14 × 10 − 9, χ2 = 34.1, OD = 2.2). The study identified three protective haplotypes (TAAG p = 1.00 × 10 − 4; AGTA p = 0.022 and GGGCC p = 0.0175) and a risk haplotype (TGGA p = 2.86 × 10 − 10) for the development of CAD. This study is in line with others that indicated that the SNPs located in the intronic region of the CDKN2B-AS1 gene are associated with CAD.
Highlights
Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide and represents a tremendous social and economic burden on society [1]
Recent genome-wide association studies have indicated that there is an association between the increased susceptibility to CAD and specific single nucleotide polymorphisms (SNPs) within the genome [3,4,5,6,7] which play a role in conjunction with other known traditional CAD risk factors
In comparing two multivariate models built with and without CAD-associated SNPs, we found these risk SNPs adding predictive value of CAD on top of known risk factors such as age, gender, and body mass index (BMI)
Summary
Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide and represents a tremendous social and economic burden on society [1]. Genome-wide association studies (GWAS) have reported the increased susceptibility to CAD in carriers of certain single nucleotide polymorphisms (SNPs) within chromosome 9p21.3 locus [3,4,5,6,7]. This locus codes for an anti-sense RNA (CDKN2B-AS1 or ANRIL), which is located nearby the CDKN2A-CDKN2B gene cluster [8,9,10]. Studies conducted on the population of the Eastern Province of Saudi Arabia have reported that 59.2% of sudden death incidences are attributable to CAD [29]. We carried out a case-control study to investigate the association of 12 risk variants at 9p21.3 locus with myocardial infarction (MI) in a Saudi Arabian population for the first time
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