Variants on Chromosome 9p21 Confer Risks of Noncardioembolic Cerebral Infarction and Carotid Plaque in the Chinese Han Population

Abstract

AIMS: Considering that cerebral infarction (CI) may share a common etiological basis with coronary artery disease (CAD), we evaluated six CAD-related single-nucleotide polymorphisms (SNPs) on 9p21 for investigating the effect of 9p21 on CI or carotid plaque in the Chinese Han population. METHODS: Altogether, 528 patients with noncardioembolic CI (375 with carotid plaque and 153 without carotid plaque) and 258 control subjects were genotyped. Six SNPs previously shown to be associated with CAD were sequenced and assessed for association with CI and carotid plaque using odds ratio (OR) and 95% confidence interval (CI) from logistic regression models. RESULTS: The G allele frequencies of rs2383206 (OR=1.472, p=0.021) and rs4977574 (OR=1.519, p=0.013) significantly increased in patients with CI without carotid plaque compared with middle-aged patients in the control group. The CI risk was higher among the GG genotype carriers than among GA ＋ AA genotype carriers (OR=1.794, 95% CI=1.059-3.039, p=0.030 for rs2383206; OR=1.866, 95% CI=1.088-3.201, p=0.023 for rs4977574). In comparison with the non-GG genotype, the GG genotype of rs2383206 and rs4977574 combined had a 1.733-fold greater risk of CI in the middle-aged group. SNPs rs2383206 and rs4977574 were also associated with a risk of carotid plaque among patients with CI aged ＞ 65 years (OR=2.329, p=0.018 and OR=1.997, p=0.049, respectively). Moreover, six SNPs were strongly correlated with linkage disequilibrium. CONCLUSIONS: Genetic variations of rs2383206 and rs4977574 on 9p21 are potentially associated with CI and carotid plaque in the Chinese Han population. Our results provide further evidence that the 9p21 region represents a major risk locus for cerebrovascular diseases.