Genome-wide association study validation identifies novel loci for atherosclerotic cardiovascular disease
Genome-wide association study validation identifies novel loci for atherosclerotic cardiovascular disease
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DOI：
10.1111/j.1538-7836.2012.04815.x
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发表时间：
2012-08-01
影响因子：
10.4
通讯作者：
Wang, X.
中科院分区：
文献类型：
--
作者：
Chen, X.;Li, S.;Wang, X.
背景资料：最近的全基因组关联研究（GWAS）已经确定了影响血脂水平和冠状动脉疾病（CAD）风险的遗传变异。目的：检测GWAS中与脂蛋白代谢和CAD相关的单核苷酸多态性（SNP）与动脉粥样硬化性心血管疾病（ASCVD，包括缺血性卒中[IS]和心肌梗死[MI]表型）的相关性。患者和方法：在中国汉族人群中进行了两阶段遗传关联研究。第一阶段包括一个队列，451例IS病例和462例对照，使用92个SNP进行关联分析。第二阶段在779例IS病例和836例对照组以及824例MI病例和737例对照组中检查了8种阳性变异和5种其他变异与IS、MI和ASCVD的相关性。结果如下：位于KLF 14基因附近的rs 4731702的T等位基因与MI风险降低相关，比值比（OR）为0.72（P < 3.85 x 10-3）。rs 4731702-T等位基因也与ASCVD风险降低相关，OR为0.78（P < 5.43 x 10-4）。此外，我们发现KLF 14的一个错义变体rs 111400400（Ser 58 Pro）与MI相关。结论：KLF 14基因附近/内部新发现的遗传变异与动脉粥样硬化相关表型的病因学有关。
Background: Genetic variants influencing lipid levels and risk of coronary artery disease (CAD) have been identified by recent genome-wide association studies (GWAS). Objectives: To test the association of single nucleotide polymorphisms (SNPs) implicated in lipoprotein metabolism and CAD in GWAS with atherosclerotic cardiovascular disease (ASCVD, including ischemic stroke [IS] and myocardial infarction [MI] phenotypes). Patients and methods: A two-stage genetic association study was conducted in the Chinese Hans population. Stage I included a cohort with 451 IS cases and 462 controls for association analysis using 92 SNPs. Stage II examined the associations of eight positive variants and five additional variants with IS, MI and ASCVD in a cohort with 779 IS cases and 836 controls and a cohort with 824 MI cases and 737 controls. Results: The T allele of rs4731702 located near the KLF14 gene was associated with a decreased risk of MI with an odds ratio (OR) of 0.72 (P < 3.85 x 10-3). The rs4731702-T allele was also associated with a decreased risk of ASCVD with an OR of 0.78 (Pmeta-analysis < 5.43 x 10-4). In addition, we found that a missense variant of KLF14, rs111400400 (Ser58Pro), was associated with MI. Conclusion: Genetic variants newly identified near/in the KLF14 gene were implicated in the aetiology of atherosclerotic-related phenotypes.