Notch3基因多态、MTHFR基因多态和ALOX5AP基因多态的多位点联合交互作用显著增加血栓性脑卒中的风险  

Interaction of Variants in Notch3 gene,MTHFR gene and ALOX5AP gene Significantly Increase the Risk for Thrombotic Stroke

作　　者：刘峻豪[1] 孙凯[1] 白永怿[1] 汪一波[1] 张伟丽[1] 陈敬洲[1] 王虎[1] 宋晓东[1] 惠汝太 

机构地区：[1]中国医学科学院 中国协和医科大学 阜外心血管病医院 中德实验室,100037

出　　处：《中国分子心脏病学杂志》2008年第6期328-332,共5页Molecular Cardiology of China

基　　金：国家973重点基础研究发展规划资助项目(G200056901)

摘　　要：目的研究Notch3基因、MTHFR基因和ALOXSAP基因多态之间的多位点交互作用是否与脑卒中的患病风险相关。方法采用病例对照设计,对来自全国7个临床中心的对照和脑卒中患者检测了Notch3、MTHFR、VKORC1、APOA1和ALOX5AP基因的8个多态性,基因分型结果经测序进一步确证。用Generalized Multifactor-Dimensionality Reduction(GMDR)方法检测基因与基因之间的交互作用。结果当个体同时携带Notch3 381TT、MTHFR 677TT和ALOX5AP 2354AA基因型时,携带者血栓性脑卒中的相对患病风险率增加至3.72倍(95%CI:1.235～11.209;P<0.05)。结论Notch 3 381TT、MTHFR 677TT和ALOX5AP 2354AA基因型的多位点联合交互作用显著增加血栓性脑卒中患病风险。对基因与基因之间的交互作用的分析,有助于更深入的研究复杂疾病的基因型和表型间的关系。AIM This study was to explore possible interactions among genetic risk factors for stroke risk. Methords We randomly recruited a total of 4000 ethnically identical participants from 7 clinical centers and examined 8 variants in 5 candidate genes for stroke risk. Interactions were explored by using the methods of generalized muhifactor dimensionality reduction （GMDR）. Results The GMDR analysis showed a significant gene-gene interaction among Notch3 C381T, MTHFR C677T and ALOX5AP T2354. The combination of MTHFR 677TT/ALOX5AP 2354AA/Notch3 381TT contributed to a significantly higher risk of thrombotic stroke （ OR, 3. 720 ; 95% CI, 1. 235 to 11. 209 ; P 〈 0.05） than did any one of the variant. Conclusion The three-loci interaction significantly confers higher risk for thrombotic stroke. Such combinational analysis could be helpful to explore genetic risk factors of common complex diseases.

关 键 词：GMDR方法 遗传 多态性 交互作用 脑卒中 

分 类 号：R743.3[医药卫生—神经病学与精神病学]