Genetic Variant rs10757278 on Chromosome 9p21 Contributes to Myocardial Infarction Susceptibility

Abstract

Large-scale genome-wide association studies (GWAS) have revealed that rs10757278 polymorphism (or its proxy rs1333049) on chromosome 9p21 is associated with myocardial infarction (MI) susceptibility in individuals of Caucasian ancestry. Following studies in other populations investigated this association. However, some of these studies reported weak or no significant association. Here, we reevaluated this association using large-scale samples by searching PubMed and Google Scholar databases. Our results showed significant association between rs10757278 polymorphism and MI with p = 6.09 × 10−22, odds ratio (OR) = 1.29, 95% confidence interval (CI) 1.22–1.36 in pooled population. We further performed a subgroup analysis, and found significant association between rs10757278 polymorphism and MI in Asian and Caucasian populations. We identified that the association between rs10757278 polymorphism and MI did not vary substantially by excluding any one study. However, the heterogeneity among the selected studies varies substantially by excluding the study from the Pakistan population. We found even more significant association between rs10757278 polymorphism and MI in pooled population, p = 3.55 × 10−53, after excluding the study from the Pakistan population. In summary, previous studies reported weak or no significant association between rs10757278 polymorphism and MI. Interestingly, our analysis suggests that rs10757278 polymorphism is significantly associated with MI susceptibility by analyzing large-scale samples.

Association of the genetic markers for myocardial infarction with sudden cardiac death

“…The results demonstrated that the association with IHD was more pronounced in the individuals before 55 years old and in women 11 . Recent large-scale meta-analysis suggests that rs10757278 (or its proxy rs1333049) polymorphism is significantly associated with MI again 29 . According to the results of our study male carriers of the genotype GG rs10757278 and CC genotype rs1333049 have an increased risk of SCD.…”

“… 11 Recent large-scale meta-analysis suggests that rs10757278 (or its proxy rs1333049) polymorphism is significantly associated with MI again. 29 According to the results of our study male carriers of the genotype GG rs10757278 and CC genotype rs1333049 have an increased risk of SCD. These results completely match the earlier study with a Siberian population on the association of SNPs with MI.…”

ANRILas a genetic marker for cardiovascular events in renal transplant patients - an observational follow-up cohort study

“…Among cardiovascular events, ischemic strokes showed the strongest association with ANRIL SNP rs10757278 in comparison with myocardial events. These results are supported by the univariate model for Cox regression where homozygous patients GG for ANRIL SNP rs10757278 showed a higher risk of a cardiovascular event occurring than AA or AG patients, confirming the findings of studies focusing on the general population . Moreover, the hazard ratio was higher (HR = 4.09) when only ischemic stroke was considered compared with both multiple event types (HR = 2.65).…”

Association of rs10811656 on 9P21.3 with the risk of coronary artery disease in a Chinese population

“…This genomic region encodes the cyclin-dependent kinase inhibitors, CDKN2A (p16 and p14) and CDKN2B (p15) [ 4 ]. Recently, genome-wide association studies have shown that common variants in the 9p21.3 gene desert might be robustly associated with the risk of CAD, acute coronary syndrome (ACS), early atherosclerosis, abdominal aortic aneurysm, and intracranial aneurysm [ 5 – 7 ], although the mechanisms underlying these associations are not completely understood. However, it remains unknown whether rs10811656 polymorphism in this region might be linked with the risk of CAD.…”