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作 者:司斌 张舒媛 杨云云 陈宇[2] 张伟丽[2] SI Bin;ZHANG Shu-yuan;YANG Yun-yun;CHEN Yu;ZHANG Wei-li(Beijing Institute of Brain Disorders, Laboratory of Brain Disorders, Capital Medical University, Beijing 100050;State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases,CAMS & PUMC, Beijing 100037, China)
机构地区:[1]首都医科大学脑重大疾病研究中心北京脑重大疾病研究院,北京100050 [2]中国医学科学院北京协和医学院,国家心血管病中心,阜外医院,心血管疾病国家重点实验室,北京100037
出 处:《基础医学与临床》2021年第4期472-478,共7页Basic and Clinical Medicine
基 金:国家自然科学基金(81270164);国家重点基础研究发展计划(973计划)(2011CB503901)。
摘 要:目的探讨p21活化激酶2(PAK2)基因变异体rs3662C>A与卒中风险及预后的关系和机制。方法收集动脉粥样硬化性脑梗死患者733例、腔隙性脑梗死488例、脑出血435例和健康对照1727人的资料,利用logistic回归模型分析rs3662C>A与卒中风险的关系,Cox生存回归模型分析rs3662C>A与卒中预后的关系。利用荧光素酶报告基因实验分析rs3662C>A对PAK2转录活性的影响。结果与rs3662CC基因型比较,rs3662A与降低动脉粥样硬化性脑梗死的患病风险相关,比值比为0.67(95%CI:0.47~0.95,P<0.05;显性遗传模型),且主要在男性中相关。平均随访4.5年,携带rs3662A的动脉粥样硬化性脑梗死患者发生心脑血管事件和心血管病死亡的风险升高,风险比分别为1.84(95%CI:1.16~2.92,P<0.05)和2.06(95%CI:1.05~4.04,P<0.05)。rs3662C降低荧光素酶表达活性的79%(P<0.01)。结论PAK2基因rs3662A的携带者患动脉粥样硬化性脑梗死的风险低于rs3662CC携带者,但预后不良。rs3662C>A影响PAK2表达活性。Objective To identify the relationship between variant rs3662C>A in the gene of p21-activated kinase 2(PAK2)and risk of stroke as well as prognosis,and to explore the effect of rs3662C>A on the transcriptional activity of PAK2 gene.Methods In a multi-center case-control study including 733 cerebral atherothrombotic stroke,488 lacunar infarction,435 intracerebral hemorrhage and 1727 healthy controls,the relationship between variant and risk of three stroke subtypes was examined using the multivariate logistic regression model.The stroke patients were prospectively followed up for a median of 4.5 years,and the relationship between rs3662 and cardiovascularevents as well as mortality was analyzed using the Cox proportional-hazards model.The effect of rs3662C>A on the transcriptional activity of PAK2 gene was examined using the luciferase reporter assays.Results The rs3662A allele was associated with a decreased risk of atherosclerotic stroke as compared with rs3662CC genotype,and odds ratio was 0.67(95%CI:0.47~0.95,P<0.05)in a dominant genetic model.This relationship had sex-specific difference and was significant incline to male.During the follow-up,atherosclerotic stroke patients carrying with rs3662A allele had a significantly higher risk of cardio-cerebrovascular events and cardiovascular mortality;hazards ratio was respectively 1.84(95%CI:1.16~2.92,P<0.05)and 2.06(95%CI:1.05~4.04,P<0.05).The rs3662C significantly reduced the luciferase activity by 79%(P<0.01).Conclusions The carriers with rs3662A allele of PAK2 gene have a reduced risk for atherosclerotic stroke but a worse prognosis.It is found that rs3662A affects the PAK2 expression level.
关 键 词:p21活化激酶2(PAK2) 遗传变异体 易感性 卒中 预后
分 类 号:R743.3[医药卫生—神经病学与精神病学]
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