Replication of Putative Susceptibility Loci from Genome-Wide Association Studies Associated with Coronary Atherosclerosis in Chinese Han Population

Abstract

BackgroundCoronary atherosclerosis, the main cause of cardiovascular disease, is a progressive disease. Recent Genome Wide Association Studies (GWASs) discovered several novel loci associated with coronary artery disease (CAD) or its main complication myocardial infarction (MI). In this study, we investigated the associations between previously reported CAD- and MI-associated variants and coronary atherosclerosis in Chinese Han population.Methodology/Principal FindingsWe performed a case-control association study with 2,335 coronary atherosclerosis patients and 1,078 controls undergoing coronary angiography of Chinese Han from China. Fourteen single nucleotide polymorphisms (SNPs), located at 1p13.3, 1q41, 2q36.3, 6q25.1, 9p21.3, 10q11.21 and 15q22.33, were genotyped in our sample collection. Six SNPs at 9p21 were associated with coronary atherosclerosis susceptibility (Ptrend<0.05) and rs10757274 showed the most significant association (P = 2.38×10−08, OR = 1.34). These associations remained significant after adjustment for multiple comparisons. Rs17465637 at 1q41 (Ptrend = 6.83×10−03, OR = 0.86) also showed significant association with coronary atherosclerosis, but the association was not significant after multiple comparisons. Additionally, rs501120 (P = 8.36×10−03, OR = 0.80) at 10q11.21 was associated with coronary atherosclerosis in females, but did not show association in males and all participants. Variants at 1p13.3, 2q36.3, 6q25.1 and 15q22.33 showed no associations with coronary atherosclerosis and main cardiovascular risk factors in our data.Conclusions/SignificanceOur findings indicated variants at 9p21 were significantly associated with coronary atherosclerosis in Han Chinese. Variants at 1q41 showed suggestive evidence of association and variants at 10q11.21 showed suggestive evidence of association in females, which warrant further study in a larger sample.

Association between 1p13.3 genomic markers and coronary artery disease: a meta-analysis involving patients and controls

“…Our research found that SNP rs599839 showed a higher association with the CVD (OR = 1.31) in Asians. Such an association with lipid concentrations has been previously reported in a Japanese and Korean population (Xie et al, 2011). An even larger-scale case-control study in the Han Chinese population should be performed to evaluate the association of rs599839 and rs646776 with CAD susceptibility and serum lipid levels.…”

“…These populations were listed as separate data sets; all data were extracted independently by two reviewers according to the inclusion criteria. All the consistent datasets by reviewers were Samani et al, 2007;Huang et al, 2008;Muendlein et al, 2009;MIGen Consortium, 2009;Wang et al, 2011;Xie et al, 2011;Guo et al, 2011;Ellis et al, 2011;Gigante et al, 2012;Esparragón et al, 2012;Lee et al, 2013. Discrepancies were recorded and solved by discussion with a third reviewer.…”

“…Finally, 12 studies (17,766 patients and 20,272 controls) were included in this meta-analysis. Of these, 2 studies were performed in Oceania (Ellis et al, 2011), 7 in Europe and America (Samani et al, 2007;Muendlein et al, 2009;MIGen Consortium et al, 2009;Wang et al, 2011;Gigante et al, 2012;Esparragón et al, 2012), and 4 in Asia (Huang et al, 2008;Xie et al, 2011;Guo et al, 2011;Lee et al, 2013) (Figure 1 …”

Lack of association between the CXCL12 rs501120 polymorphism and cardiovascular disease in Spanish patients with rheumatoid arthritis

“…However, although GWAS offer powerful information, replication studies are required to validate these findings. In this regard, recent results have raised controversy regarding the role of the CXCL12 rs501120 polymorphism in the development of CV disease [13][14][15].…”

9p21 Polymorphisms increase the risk of peripheral artery disease in the Han Chinese population

“…1,11,12 The homozygous GG genotype of rs10757278 is associated with CAD severity, extent and progression in Caucasian populations, 13 and both loci are also significantly associated with ischaemic stroke risk. 9,14 The increased risk of atherosclerosis is mediated via effects on the expression of cyclin-dependent kinase inhibitor 2 A (CDKN2A, also known as INK4/ARF).…”