HDAC9 Polymorphisms Predict Susceptibility, Severity, and Short-Term Outcome of Large Artery Atherosclerotic Stroke in Chinese Population
HDAC9 Polymorphisms Predict Susceptibility, Severity, and Short-Term Outcome of Large Artery Atherosclerotic Stroke in Chinese Population
复制标题
HDAC9 多态性预测中国人群大动脉粥样硬化性卒中的易感性、严重程度和短期结果
DOI：
10.1007/s12031-018-1221-0
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发表时间：
2019-01-01
影响因子：
3.1
通讯作者：
Liu, Xinfeng
中科院分区：
文献类型：
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作者：
Wang, Mengmeng;Gu, Mengmeng;Liu, Xinfeng
最近，一项全基因组关联研究（GWAS）检测到两个组蛋白去乙酰化酶9（HDAC 9）多态性（rs 2074633和rs 28688791），这可能与大动脉粥样硬化（LAA）卒中的风险相关。本研究旨在调查这两个多态性是否与中国南方汉族人群左心耳卒中的易感性、严重程度和短期预后相关。采用SNPscan技术对1011例LAA卒中患者和1121例健康对照者进行rs 2074633和rs 28688791基因分型。入院时采用美国国立卫生研究院卒中量表（NIHSS）评分，卒中发作后3个月采用改良兰金量表评分，分别评估入院时卒中严重程度和短期预后。rs 2074633（P = 0.039）和rs 28688791（P = 0.025）与LAA卒中风险相关。在根据性别和年龄进行的亚组分析中，仅在男性（rs 2074633的P = 0.029; rs 28688791的P = 0.013）和< 60岁的成年人（rs 2074633的P = 0.009; rs 28688791的P = 0.003）中发现了这种风险增加。此外，我们检测到这两个多态性和年龄之间的显着交互作用（Pinteraction= 0.027 rs 2074633; Pinteraction= 0.044 rs 28688791）。rs 28688791的CC基因型（P = 0.037）也与中度和重度脑卒中（NIHSS ≥ 6）相关。此外，rs 2074633和rs 28688791的CC基因型（rs 2074633，P = 0.019; rs 28688791，P = 0.023）显示与左心耳卒中的不良短期结局显著相关。我们的研究结果表明HDAC 9多态性可作为LAA卒中易感性、严重程度和短期预后的生物标志物。
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 (Pinteraction= 0.027 for rs2074633; Pinteraction= 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.