Intronic Polymorphisms in the CDKN2B-AS1 Gene Are Strongly Associated with the Risk of Myocardial Infarction and Coronary Artery Disease in the Saudi Population

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, χ 2 = 4.6, odds ratio (OD) = 1.5; rs4977574 p = 0.0336, χ 2 = 4.5, OD = 1.4; rs2891168 p = 1.85ˆ10´10, χ 2 = 40.6, OD = 2.1 and rs1333042 p = 5.14ˆ10´9, χ 2 = 34.1, OD = 2.2). The study identified three protective haplotypes (TAAG p = 1.00ˆ10´4; AGTA p = 0.022 and GGGCC p = 0.0175) and a risk haplotype (TGGA p = 2.86ˆ10´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.

Long noncoding RNA CDKN2B‐AS1 interacts with transcription factor BCL11A to regulate progression of cerebral infarction through mediating MAP4K1 transcription

“…Chen et al (33) found that the polymorphism of CDKN2B-AS is very likely to be linked to intracranial aneurysm in Chinese population. Additionally, single nucleotide polymorphisms found in the intronic region of CDKN2B-AS1 have been revealed to be linked to coronary artery diseases (14). These findings are consistent with our results revealing elevated levels of lncRNA CDKN2B-AS1 in cerebral infarction lymphocytes, which may serve as a biomarker for cerebral infarction.…”

“…Aberrant expression of lncRNA CDKN2B-AS1 has been reported to predict lung cancer (11). Furthermore, previous studies have indicated correlations between genetic variants of lncRNA CDKN2B-AS1 genetic variants and cardiovascular diseases and stroke (12)(13)(14). However, the underlying mechanism of lncRNA CDKN2B-AS1 in the pathogenesis of stroke remains largely unknown.…”

Chromosome 9p21 and ABCA1 Genetic Variants and Their Interactions on Coronary Heart Disease and Ischemic Stroke in a Chinese Han Population

“…[ 13 ] illustrated that heritability was 37.9% for all IS, 40.3% for large-vessel disease, 32.6% for cardio-embolic, and 16.1% for small-vessel disease. Although data accumulated from previous studies have identified associations between SNPs on chromosome 9p21 and the risk of CHD [ 14 , 15 , 16 , 17 , 18 ] and IS [ 19 , 20 ] in Caucasians, little is known about such associations among the Chinese populations. Moreover, many SNPs have still not been detected on the chromosome 9p21 region.…”

9P21.3 locus; An Important Region in Coronary Artery Disease: A Panel Approach to Investigation of the Coronary Artery Disease Etiology

“…Among these variants, rs2383206 and rs10757278 displayed the closest association with CAD in an Indian population [127,128]. Investigation of CAD in a Saudi population identified four SNPs including rs564398, rs4977574, rs2891168, and rs1333042 associated with CAD/MI [129]. The first large case-control study (PROMIS) of a Pakistan population concluded that six (rs1333049, rs10757274, rs4977574, rs2891168, rs1537372 and rs9632885) of eighty-nine investigated SNP in the 9p21.3 locus were associated with MI [130].…”