title: HDAC9 Variant Rs2107595 Modifies Susceptibility to Coronary Artery Disease and the Severity of Coronary Atherosclerosis in a Chinese Han Population.
abstract: 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.
authors: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors: Xue-Bin
authors: XB
authors: Wang
authors: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors: Ya-di
authors: YD
authors: Han
authors: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors: Shrestha
authors: S
authors: Sabina
authors: Department of Clinical Laboratory, Children's Hospital of Zhengzhou, Zhengzhou, Henan, China.
authors: Ning-Hua
authors: NH
authors: Cui
authors: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors: Shuai
authors: S
authors: Zhang
authors: Center of Clinical Laboratory, Wuhan Asia Heart Hospital, Wuhan, Hubei, China.
authors: Ze-Jin
authors: ZJ
authors: Liu
authors: Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, China.
authors: Cong
authors: C
authors: Li
authors: Center for Gene Diagnosis, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, China.
authors: Fang
authors: F
authors: Zheng
mesh_terms: D000483:Alleles; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China; D003324:Coronary Artery Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006655:Histone Deacetylases / Q000097:blood / Q000235:genetics*; D006801:Humans; D009203:Myocardial Infarction / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D012097:Repressor Proteins / Q000097:blood / Q000235:genetics*
chemical_list: D012097:Repressor Proteins; C486544:HDAC9 protein, human; D006655:Histone Deacetylases