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The same chromosome 9p21.3 locus is associated with type 2 diabetes and coronary artery disease in a Chinese Han population.

ABSTRACT: OBJECTIVE: Recent genome-wide association studies (GWAS) revealed that a 9p21.3 locus was associated with type 2 diabetes. In this study, we carried out a large-scale case-control study in the GeneID Chinese Han population to 1) further replicate the association of 9p21.3 type 2 diabetes GWAS single nucleotide polymorphisms (SNPs) and 2) assess the association of these SNPs with coronary artery disease. RESEARCH DESIGN AND METHODS: Three SNPs (rs2383208, rs10811661, and rs10757283) were genotyped in two GeneID cohorts of 3,167 Chinese Han individuals. Case-control association design was used to determine the association of the SNPs with type 2 diabetes and coronary artery disease. Gensini scores were calculated in the coronary artery disease subjects and were tested for association with the variants. Multivariate logistic regressions were performed on association studies. RESULTS: The association between two of the three SNPs and type 2 diabetes was replicated in the GeneID population (rs2383208, P = 0.936; rs10811661-T, P = 0.02, odds ratio [OR] = 1.23; rs10757283-C, P = 0.003, OR = 1.30). The same two SNPs also contributed to the risk of coronary artery disease (CAD) (rs10811661-T, P = 0.002, OR = 1.19; rs10757283-C, P = 0.003, OR = 1.18). In addition, rs10757283 was associated with severity of coronary atherosclerosis estimated by the Gensini scoring system (risk allele C, quantitative-trait regression adjusted P = 0.002). CONCLUSIONS: For the first time to our knowledge, our results indicated that the same 9p21.3 locus, represented by SNPs rs10811661 and rs10757283, contributed to the risk of type 2 diabetes and coronary artery disease in our GeneID Chinese Han population.

SUBMITTER: Cheng X

PROVIDER: S-EPMC3028370 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature

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The same chromosome 9p21.3 locus is associated with type 2 diabetes and coronary artery disease in a Chinese Han population.

Cheng Xiang X Shi Lisong L Nie Shaofang S Wang Fan F Li Xiuchun X Xu Chengqi C Wang Pengyun P Yang Baofeng B Li Qingxian Q Pan Zhenwei Z Li Yue Y Xia Hao H Zheng Chenhong C Ke Yuhe Y Wu Yanxia Y Tang Tingting T Yan Xinxin X Yang Yan Y Xia Ni N Yao Rui R Wang Binbin B Ma Xu X Zeng Qiutang Q Tu Xin X Liao Yuhua Y Wang Qing K QK

Diabetes 20110201 2

<h4>Objective</h4>Recent genome-wide association studies (GWAS) revealed that a 9p21.3 locus was associated with type 2 diabetes. In this study, we carried out a large-scale case-control study in the GeneID Chinese Han population to 1) further replicate the association of 9p21.3 type 2 diabetes GWAS single nucleotide polymorphisms (SNPs) and 2) assess the association of these SNPs with coronary artery disease.<h4>Research design and methods</h4>Three SNPs (rs2383208, rs10811661, and rs10757283) ...[more]

PMID: 21270277

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Project description:The aim of the present study was to investigate the susceptibility of two coronary artery disease (CAD)-associated single nucleotide polymorphisms on 9p21 (rs1333049 and rs10757278) to myocardial infarction (MI) in a primary (stratification of high risk group for MI) and secondary prevention setting. The prospective observational study included 500 patients with MI [411 males (82.2%) and 89 females (17.8%)] under 65 years. The risk of MI for carriers of the homozygous CC genotype of rs1333049 and homozygous GG genotype of rs10757278 was 1.77 [95% confidence interval (CI): 1.36-2.37], and 1.70 (95% CI: 1.24-2.32) respectively. The risk of MI for heterozygous allele carriers was slightly lower. Specifically, the risk of MI was 1.58 (95% CI: 1.18-2.11) for both heterozygous and homozygous carriers of the rs1333049 C allele, and 1.36 (95% CI: 1.01-1.83) for the carriers of the rs10757278 G allele. A logistic regression model including sex, age, presence of excess weight or obesity, abdominal obesity, diabetes mellitus, arterial hypertension, hypercholesterolemia, positive family history and smoking status parameters revealed that rs1333049 CC genotype was an independent predictive factor of myocardial infraction [OR=1.71 (95% CI: 1.16-2.52), P=0.006]. Patients who underwent percutaneous coronary intervention (PCI) during index hospitalization and patients who did not receive PCI were followed up for two years after discharge. Compared with patients with MI who underwent PCI, the risk of recurrent acute coronary syndrome (re-ACS) was higher among rs1333049 C allele carriers who did not receive PCI during index hospitalization. One year after MI, the OR of re-ACS was 4.91 (95% CI: 1.45-16.66), while two years after MI, OR was 3.77 (95% CI: 1.50-9.52) in those patients who did not receive PCI during index hospitalization. There was no statistically significant association between polymorphic variants of rs1333049 and MI follow-up outcomes in patients who underwent PCI. The present study indicated clinical utility of 9p21.3 genotyping to predict the outcomes for patients with MI without PCI. Due to the small sample size, this association study forms basis for larger, nationwide studies investigating clinical applications of genetic data.

Dataset Information

The same chromosome 9p21.3 locus is associated with type 2 diabetes and coronary artery disease in a Chinese Han population.

Publications

The same chromosome 9p21.3 locus is associated with type 2 diabetes and coronary artery disease in a Chinese Han population.

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