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.
Highlights
Coronary atherosclerosis is a progressive disease and the potential consequences in atherosclerosis include: coronary artery disease (CAD) and its main complication myocardial infarction (MI)
Among the 14 single nucleotide polymorphisms (SNPs), rs17228212 with a minor allele frequency (MAF) of less than 1% was removed from further association analysis
Twelve SNPs conformed to Hardy-Weinberg equilibrium (HWE) were investigated association in 2,335 coronary atherosclerosis patients and 1,078 control subjects
Summary
Coronary atherosclerosis is a progressive disease and the potential consequences in atherosclerosis include: coronary artery disease (CAD) and its main complication myocardial infarction (MI). During the past five decades, large-scale epidemiological studies and genetic association analysis have identified multiple risk factors and susceptibility genes for coronary atherosclerosis [4]. Variants of several functionally important genes, including ApoE [5] and LDLR [6], have been implicated in susceptibility to coronary atherosclerosis in general population. Recent GWASs and meta-analysis in CAD and MI identified several new susceptibility loci [7,8,9,10,11,12] Among these loci, the strongest association signals were on chromosome 9p21.3, which were correlated with stroke, abdominal aortic and intracranial aneurysms in several other cohorts [13]. Recent Genome Wide Association Studies (GWASs) discovered several novel loci associated with coronary artery disease (CAD) or its main complication myocardial infarction (MI). We investigated the associations between previously reported CADand MI-associated variants and coronary atherosclerosis in Chinese Han population
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