HDAC9 Polymorphisms Predict Susceptibility, Severity, and Short-Term Outcome of Large Artery Atherosclerotic Stroke in Chinese Population

Recently, a genome-wide association study (GWAS) detected two histone deacetylase 9 (HDAC9) polymorphisms (rs2074633 and rs28688791) which may be associated with risk of large artery atherosclerotic (LAA) stroke. This study aimed to investigate whether these two polymorphisms were associated with susceptibility, severity, and short-term outcome of LAA stroke in a southern Chinese Han population. rs2074633 and rs28688791 were genotyped using SNPscan technology in 1011 LAA stroke patients and 1121 healthy controls. Stroke severity on admission and short-term outcome were, respectively, assessed by the National Institute of Health Stroke Scale (NIHSS) score on admission and modified Rankin Scale score at 3 months after stroke onset. rs2074633 (P = 0.039) and rs28688791 (P = 0.025) were associated with risk of LAA stroke. In subgroup analysis according to sex and age, this increased risk was only found in males (P = 0.029 for rs2074633; P = 0.013 for rs28688791) and adults aged < 60 years (P = 0.009 for rs2074633; P = 0.003 for rs28688791). Moreover, we detected significant interactions between these two polymorphisms and age (P_interaction = 0.027 for rs2074633; P_interaction = 0.044 for rs28688791). The CC genotype of rs28688791 (P = 0.037) was also associated with moderate and severe stroke (NIHSS ≥ 6). Additionally, the CC genotype of rs2074633 and rs28688791 (rs2074633, P = 0.019; rs28688791, P = 0.023) showed significant association with unfavorable short-term outcome of LAA stroke. Our results indicated that HDAC9 polymorphisms may be used as biomarkers for susceptibility, severity, and short-term outcome of LAA stroke.