HDAC9 Variant Rs2107595 Modifies Susceptibility to Coronary Artery Disease and the Severity of Coronary Atherosclerosis in a Chinese Han Population

• Published in: PloS one Vol. 11; no. 8; p. e0160449
• Main Authors: Wang, Xue-Bin, Han, Ya-di, Sabina, Shrestha, Cui, Ning-Hua, Zhang, Shuai, Liu, Ze-Jin, Li, Cong, Zheng, Fang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.08.2016; Public Library of Science (PLoS)
• Subjects: Alleles; Analysis; Angina; Angina pectoris; Arteriosclerosis; Asian Continental Ancestry Group - genetics; Atherosclerosis; Binding sites; Biology and Life Sciences; Body mass; Body mass index; Body size; Cardiovascular disease; Case-Control Studies; Cerebral infarction; China; Coronary artery; Coronary artery disease; Coronary Artery Disease - genetics; Coronary heart disease; Coronary vessels; Correlation analysis; Diabetes; Diabetes mellitus; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - genetics; Disease susceptibility; Ecological risk assessment; Gene expression; Gene polymorphism; Gene-Environment Interaction; Genes; Genetic aspects; Genetic Predisposition to Disease; Genome-wide association studies; Genomes; Genotypes; Health risk assessment; Health risks; Heart attacks; Heart diseases; Hepatitis; Histone deacetylase; Histone Deacetylases - blood; Histone Deacetylases - genetics; Hospitals; Humans; Hyperlipidemia; Hypertension; Laboratories; Lipids; Medicine and Health Sciences; Metabolism; Myocardial infarction; Myocardial Infarction - genetics; Pathogenesis; Patients; Physiological aspects; Polymorphism; Polymorphism, Single Nucleotide; Population; Repressor Proteins - blood; Repressor Proteins - genetics; Risk analysis; Risk factors; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Stroke; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0160449

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.