北京市房山区缺血性脑卒中表型不一致同胞对的遗传流行病学研究

目的:探讨血脂、血压水平以及肝脂酶基因(LIPC)-514C/T多态性与缺血性脑卒中及其亚型在表型不一致同胞对之间的关联.方法:采用先证者引荐的方法,通过以社区为基础的卫生服务系统收集家系.用广义估计方程(generalized estimating equation, GEE)对表型不一致同胞对进行多因素相关分析,并采用以家系为基础的关联检验(family based association test, FBAT)的方法进行关联分析.结果:对71个缺血性脑卒中患病家系所组成的107对表型不一致同胞对进行单因素和多因素的GEE分析,均提示血压和血脂水平增高与缺血性脑卒中的发病危险存在相关性(P＜0.05).大动脉粥样硬化型缺血性脑卒中比小动脉闭塞型缺血性脑卒中具有更高的血脂水平;而小动脉闭塞型缺血性脑卒中病例具有更高的舒张压水平.采用FBAT方法发现在加性遗传模型中LIPC基因-514T等位基因与低密度脂蛋白胆固醇(LDL-C)以及舒张压水平之间存在关联(Z=2.366,P＜0.05),调整年龄、性别、吸烟、饮酒、肥胖程度等变量后,LIPC基因-514T等位基因与舒张压水平仍然存在关联(加性遗传模型Z=-2.277,P＜0.05;隐性遗传模型Z=-2.244,P＜0.05),但并未发现其与缺血性脑卒中及各亚型之间的关联.结论:在所收集家系的表型不一致同胞对中,血压和血脂异常均可使缺血性脑卒中发病危险增加,不同亚型的缺血性脑卒中发病机制可能存在差异.LIPC基因-514T等位基因与LDL-C以及舒张压水平之间可能存在关联.

Genetic epidemiological study on discordant sib pairs of ischemic stroke in Beijing Fangshan District

Objective:To investigate the association among serum lipids,blood pressure,-514C/T polymorphism of hepatic lipase gene and subtypes of ischemic stroke in the discordant sib pairs.Methods:Ischemic stroke cases were enrolled from a hospital-based stroke registry,the proband-initiated contact was used to recruit pedigrees,and participants' information and blood samples were collected through the community-based health care networks in rural areas of China.Statistical analysis was performed by using the Wilcoxon signed rank test to compare quantitative differences between sib pairs and the McNemar test to compare qualitative differences.Generalized estimating equation(GEE)was used to adjust for within-family correlation in analysis of discordant sib pairs.Family based association test(FBAT)was applied to associations between serum lipids,blood pressure and the-514T allele in hepatic lipase gene.Results:Totally 107 discordant sib pairs from 71 ischemic stroke patients pedigrees were analyzed by univariate and multivariate methods.The blood pressure and serum lipids were associated with ischemic stroke.(P<0.05)The lipid level was higher in large-artery atherosclerosis ischemic stroke than in the subtype of small-vessel occlusion,while the blood pressure was higher in the latter.The-514T allele in hepatic lipase gene was associated with low density lipoprotein-cholesterol(LDL-C)and diastolic blood pressure in additive model by FBAT analysis(Z=2.366,P<0.05),and it was also associated with diastolic blood pressure in additive model(Z=-2.277,P<0.05)and recessive model(Z=-2.244,P<0.05),but not associated with ischemic stroke or its subtypes.Conclusion:In these discordant sib pairs,the abnormalities of blood pressure and serum lipids may increase risks of ischemic stroke,and different subtypes of ischemic stroke may differ from each other in etiology.The-514T allele in hepatic lipase gene may be associated with LDL-C and diastolic blood pressure.