HDAC9 Variant Rs2107595 Modifies Susceptibility to Coronary Artery Disease and the Severity of Coronary Atherosclerosis in a Chinese Han Population.
HDAC9 Variant Rs2107595 Modifies Susceptibility to Coronary Artery Disease and the Severity of Coronary Atherosclerosis in a Chinese Han Population.
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HDAC9 变异体 Rs2107595 改变中国汉族人群对冠状动脉疾病的易感性和冠状动脉粥样硬化的严重程度
DOI：
10.1371/journal.pone.0160449
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Zheng F
中科院分区：
文献类型：
--
作者：
Wang XB;Han YD;Sabina S;Cui NH;Zhang S;Liu ZJ;Li C;Zheng F
之前的一项全基因组关联研究表明，组蛋白脱乙酰酶 9 (HDAC9) 基因中的单核苷酸多态性 (SNP) rs2107595 与白种人的大动脉卒中 (LAS) 相关。基于LAS与冠状动脉疾病（CAD）之间相似的动脉粥样硬化发病机制，我们旨在评估中国汉族人群中SNP rs2107595与CAD风险和冠状动脉粥样硬化严重程度的关联，并探讨SNP rs2107595与传统CAD危险因素之间潜在的基因-环境相互作用。在一项共有 2317 名 CAD 患者和 2404 名对照者的两阶段病例对照研究中，SNP rs2107595 的 AG + AA 基因型与 CAD 风险增加（调整后优势比 (OR) = 1.23，Padj = 0.001）和更高的修改 Gensini 评分（调整后 OR = 1.38，Padj < 0.001）显着相关。这些关联在不稳定心绞痛 (UAP)、非 ST 段抬高型心肌梗死 (NSTEMI) 和 ST 段抬高型心肌梗死 (STEMI) 的亚型分析中仍然显着。亚组和多因素降维分析（MDR）进一步发现SNP rs2107595、体重指数、2型糖尿病和高脂血症之间的基因-环境相互作用与CAD风险和冠状动脉粥样硬化的严重程度有关。此外，CAD 患者的 HDAC9 mRNA 表达水平和血浆 HDAC9 水平高于对照组。随后的基因型-表型分析观察到 SNP rs2107595 与对照组和 NSTEMI 和 STEMI 患者的 HDAC9 mRNA 表达和血浆 HDAC9 水平显着相关。综上所述，我们的数据表明，SNP rs2107595 可能通过调节 HDAC9 表达和基因-环境相互作用的可能机制，导致冠状动脉粥样硬化和 CAD 风险。
A previous genome-wide association study showed that a single nucleotide polymorphism (SNP) rs2107595 in histone deacetylase 9 (HDAC9) gene was associated with large artery stroke (LAS) in Caucasians. Based on the similar atherosclerotic pathogenesis between LAS and coronary artery disease (CAD), we aimed to evaluate the associations of SNP rs2107595 with CAD risk and the severity of coronary atherosclerosis in a Chinese Han population, and explore the potential gene-environment interactions among SNP rs2107595 and conventional CAD risk factors. In a two-stage case-control study with a total of 2317 CAD patients and 2404 controls, the AG + AA genotypes of SNP rs2107595 were significantly associated with increased CAD risk (Adjusted odds ratio (OR) = 1.23, Padj = 0.001) and higher modified Gensini scores (Adjusted OR = 1.38, Padj < 0.001). These associations remained significant in subtype analyses for unstable angina pectoris (UAP), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). Subgroup and multifactor dimensionality reduction analyses (MDR) further found the gene-environment interactions among SNP rs2107595, body mass index, type 2 diabetes and hyperlipidemia in CAD risk and the severity of coronary atherosclerosis. Moreover, patients with CAD had higher levels of HDAC9 mRNA expression and plasma HDAC9 than controls. Subsequent genotype-phenotype analyses observed the significant correlations of SNP rs2107595 with HDAC9 mRNA expression and plasma HDAC9 levels in controls and patients with NSTEMI and STEMI. Taken together, our data suggest that SNP rs2107595 may contribute to coronary atherosclerosis and CAD risk through a possible mechanism of regulating HDAC9 expression and gene-environment interactions.
有效的蒙特卡洛置换测试，用于基因型缺失的遗传病例对照研究。
影响因子：
2.1
作者：
Kinnamon DD;Martin ER
通讯作者：
Martin ER