白三烯A4水解酶基因多态性与缺血性脑卒中的关联研究

武轶群; 李帅; 刘括; 唐迅; 方凯; 李娜; 李劲; 吴涛; 陈大方; 胡永华

Abstract

武轶群,李帅,刘括,唐迅,方凯,李娜,李劲,吴涛,陈大方,胡永华.白三烯A4水解酶基因多态性与缺血性脑卒中的关联研究[J].Chinese journal of Epidemiology,2015,36(8):786-789

白三烯A4水解酶基因多态性与缺血性脑卒中的关联研究

Study on the association between leukotriene A4 hydrolase gene polymorphism and ischemic stroke

Received:January 29, 2015

DOI：10.3760/cma.j.issn.0254-6450.2015.08.003

KeyWord: 脑卒中, 缺血性白三烯A4水解酶单核苷酸多态性遗传流行病学

English Key Word: Ischemic stroke Leukotriene A4 hydrolase Single nucleotide polymorphism Genetic epidemiology

FundProject:国家自然科学基金(81172744, 81230066);教育部博士点基金(20120001120029)

Author Name	Affiliation	E-mail
Wu Yiqun	Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing 100191, China
Li Shuai	Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing 100191, China
Liu Kuo	Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing 100191, China
Tang Xun	Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing 100191, China
Fang Kai	Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing 100191, China
Li Na	Fangshan Science and Technology Committee
Li Jin	Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing 100191, China
Wu Tao	Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing 100191, China
Chen Dafang	Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing 100191, China
Hu Yonghua	Department of Epidemiology and Biostatistics, Peking University Health Science Center, Beijing 100191, China	yhhu@bjmu.edu.cn

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Abstract:

目的探讨白三烯A4水解酶(LTA4H)基因多态性与缺血性脑卒中(IS)及其亚型的关联性。方法采用表型不一致同胞对研究设计, 分析4个LTA4H基因单核苷酸多态性位点(rs2072512、rs2540489、rs2540500和rs6538697)与IS及其亚型的关联关系。采用广义估计方程(GEE)进行多因素分析, 采用条件logistic回归模型和以家系为基础的关联检验(FBAT)进行关联分析。结果对234个家系所组成的356对表型不一致同胞对进行分析, 发现高血压、糖尿病、高脂血症的患病情况与IS的发病风险存在相关。各位点与IS的关联分析发现, 在加性和隐性模型下, rs2540489基因型与IS的关联具有统计学意义, G等位基因是保护因素(加性模型OR=0.62, 95%CI: 0.41~0.94;隐性模型OR=0.48, 95%CI: 0.23~1.02);rs2540489 基因型与大动脉粥样硬化型(LAA)IS的关联具有统计学意义, G等位基因是保护因素(加性模型OR=0.48, 95%CI: 0.24~0.95;隐性模型OR=0.25, 95%CI: 0.07~0.93);在调整年龄、性别等其他因素后, 以上关联关系仍然存在。结论 LTA4H基因 rs2540489位点多态性与大动脉粥样硬化型IS存在关联。

English Abstract:

Objective To investigate the association between polymorphism of leukotriene A4 hydrolase (LTA4H) gene among ischemic stroke patients and the related subtypes in the discordant sib pairs. Methods Families including ischemic stroke patients and their siblings were recruited. Four single nucleotide polymorphisms (SNPs) of LTA4H as rs2072512, rs2540489, rs2540500 and rs6538697 were selected. Generalized estimating equation (GEE) was used to adjust for in-family correlation in the analysis of discordant sib pairs. Conditional logistic regression model and family based association test (FBAT) were both used to test the associations of LTA4H gene with ischemic stroke and its subtypes. Results In total, data from 356 discordant sib pairs from 234 ischemic stroke patient pedigrees were analyzed. Results of GEE showed that hypertension, diabetes mellitus and hyperlipoidemia were associated with ischemic stroke. According to the association test results, rs2540489 G allele was found to be associated with ischemic stroke, both in the additive model (OR=0.62, 95%CI: 0.41-0.94) and in the recessive model (OR=0.48, 95%CI: 0.23-1.02). For two main ischemic stroke subtypes, rs2540489 G allele was found to be associated with large-artery atherosclerosis stroke in the additive model (OR=0.48, 95%CI: 0.24-0.95) and in the recessive model (OR=0.25, 95%CI: 0.07-0.93). After adjusting age, sex and other factors, the associations mentioned above, still existed. Conclusion rs2540489 polymorphism in LTA4H gene seemed to be associated with large-artery atherosclerosis stroke.

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