Association between 9p21 Genomic Markers and Ischemic Stroke Risk: Evidence Based on 21 Studies

Abstract

Epidemiological studies indicate a genetic contribution to ischemic stroke risk, but specific genetic variants remain unknown. Recently independent studies reported an association between coronary heart disease and single-nucleotide polymorphisms (SNPs) located at chromosome 9p21 (rs10757278 and proxy SNPs). Given that stroke is a common complication after myocardial infarction, several validation studies have been conducted among various ethnic populations to investigate if the same loci was associated with ischemic stroke (IS), but the results have been inconsistent. To investigate this inconsistency and derive a more precise estimation of the relationship, a meta-analysis of 34,128 cases and 153,428 controls from 21 studies was performed. Potential sources of heterogeneity including ethnicity, sample size, control source and ischemic stroke subtypes were also assessed. Overall, the summary odds ratio of IS was 1.11 (95% CI: 1.07–1.15, P<10−5) for rs10757278. In the subgroup analysis by ethnicity, significantly increased risks were found in East Asians (3188 cases and 4503 controls; OR = 1.14, 95% CI: 1.07–1.21, P<10−5) and Caucasians (30505 cases and 145153controls; OR = 1.08, 95% CI: 1.04–1.12, P<10−5) for the polymorphism; while no significant associations were found among African Americans (435 cases and 3772 controls; OR = 0.97, 95% CI: 0.63–1.51, P = 0.90) in all genetic models. In the subgroup analyses by IS subtypes, significant association was detected only in large vessel stroke group, while no significant associations among small vessel or cardioembolic stroke. When stratified by sample size, and control source, significantly increased risks were found for the polymorphism in all genetic models. This meta-analysis provides accurate and comprehensive estimates of the association of genetic variant at chromosome 9p21 and IS, but these associations vary in different ethnic populations.

Sequence Variants on Chromosome 9p21 Are Associated with Ischemic Stroke and the Lipids Level in Chinese Han Population

“…In addition, some environmental factors, which may predominate in the progress of IS and mask the effects of variation were not included in this study. 34 …”

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

“…These results are in agreement with those reported in the literature where the role of ANRIL SNP in ischemic stroke is well described. Recent meta‐analysis demonstrated that the rs10757278 SNP in ANRIL gene was a risk factor for developing ischemic stroke, particularly large‐vessel strokes but not small‐vessel or cardioembolic strokes. Our findings and previously reported studies suggest that ANRIL variants may exert more general effects on arterial wall function, such as vascular remodeling and/or repair, which is common in coronary heart disease and large‐vessel stroke.…”

Analysis on the Polymorphism of Chromosome Region 9p21 and the Susceptibility of Carotid Plaque

“…It has been determined in the past researches that the gene polymorphism of rs10757274, rs7044859, rs4977574 and rs496892 was relevant with the susceptibility of atherosclerosis-associated diseases but with some differences existing among different races [10,21,22] . In our previous study, in Chinese Han population, gene polymorphism of rs2383206 and rs4977574 in 9p21 was associated with the susceptibility of acute CI, in which the G allele was probably related to the onset of atherosclerosis-related diseases.…”

“…Currently, it has also been proved that some gene polymorphisms in 9p21 were related with the risk of carotid plaque onset in CI patients [9] . Therefore, we selected 4 susceptibility loci of atherosclerosis-associated diseases in chromosome region 9p21 confirmed by GWAS and meta-analysis to discuss the relativity between them and carotid plaque onset risk in CI patients [10,11] .…”