Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism.
Genetic variation within the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways as risk factors for venous thromboembolism.
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抗凝剂，凝血蛋白，纤维蛋白水解和先天免疫途径中的遗传变异是静脉血栓栓塞的危险因素。
DOI：
10.1111/j.1538-7836.2011.04272.x
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发表时间：
2011-06
期刊：
影响因子：
--
通讯作者：
DE Andrade M
中科院分区：
文献类型：
--
作者：
Heit JA;Cunningham JM;Petterson TM;Armasu SM;Rider DN;DE Andrade M
静脉血栓栓塞（VTE）具有高度遗传性（估计遗传率[h2]=0.62），可能是多基因作用的结果。系统地检测抗凝、促凝、纤溶和先天免疫途径中重要组分编码基因的变异，以寻找与静脉血栓栓塞的独立关联。客观诊断为静脉血栓栓塞的非西班牙裔欧洲血统成年人，以及年龄、性别组频率匹配的对照组，对764个基因中的13031个单核苷酸多态性（snp）进行基因分型。使用PLINK进行分析（n= 12296个snp），使用加性遗传模型，并根据年龄、性别、居住状态和心肌梗死或中风进行调整。在2927个个体中，ABO、F2、F5、F11、KLKB1、SELP和SCUBE1中的一个或多个snp与VTE显著相关，包括因子V Leiden、凝血酶原G20210A、ABO非o血型，以及与ABO rs2519093的新关联（or =1.68， p值=8.08×10−16），与血型无关。在分层分析中，以下基因的snp与VTE显著相关：男女中F5和ABO，女性中LY86；因子V Leiden非携带者中F2、ABO和KLKB1；ABO非o型血F5、F11、KLKB1、GFRA1；凝血酶原G20210A非携带者的ABO、F5、F11、KLKB1、SCUBE1、SELP。ABO rs2519093人群归因危险度（PAR）高于Leiden因子V和凝血酶原G20210A，且Leiden因子V和凝血酶原G20210A、ABO non-O和ABO rs2519093的联合PAR为0.40。抗凝、促凝、纤溶和先天免疫途径的遗传变异在欧洲血统的非西班牙裔成年人中占很大比例的静脉血栓栓塞。
Venous thromboembolism (VTE) is highly heritable (estimated heritability [h2]=0.62) and likely a result of multigenic action. To systematically test variation within genes encoding for important components of the anticoagulant, procoagulant, fibrinolytic and innate immunity pathways for an independent association with VTE. Non-Hispanic adults of European ancestry with objectively-diagnosed VTE, and age-, sex-group frequency matched controls were genotyped for 13,031 single nucleotide polymorphisms (SNPs) within 764 genes. Analyses (n=12,296 SNPs) were performed with PLINK using an additive genetic model and adjusted for age, sex, state of residence, and myocardial infarction or stroke. Among 2927 individuals, one or more SNPs within ABO, F2, F5, F11, KLKB1, SELP and SCUBE1 were significantly associated with VTE, including Factor V Leiden, Prothrombin G20210A, ABO non-O blood type, and a novel association with ABO rs2519093 (OR=1.68, p-value=8.08×10−16) that was independent of blood type. In stratified analyses, SNPs in the following genes were significantly associated with VTE: F5 and ABO among both genders and LY86 among women; F2, ABO and KLKB1 among Factor V Leiden non-carriers; F5, F11, KLKB1 and GFRA1 in ABO non-O blood type; and ABO, F5, F11, KLKB1, SCUBE1 and SELP among Prothrombin G20210A non-carriers. The ABO rs2519093 population-attributable risk (PAR) exceeded that of Factor V Leiden and Prothrombin G20210A, and the joint PAR of Factor V Leiden, Prothrombin G20210A, ABO non-O and ABO rs2519093 was 0.40. Anticoagulant, procoagulant, fibrinolytic and innate immunity pathway genetic variation accounts for a large proportion of VTE among non-Hispanic adults of European-ancestry.
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影响因子：
20.3
作者：
Cushman, Mary;O'Meara, Ellen S.;Heckbert, Susan R.
通讯作者：
Heckbert, Susan R.
影响因子：
30.8
作者：
Clayton, DG;Walker, NM;Todd, JA
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Todd, JA
影响因子：
168.9
作者：
Ariëns, RAS;de Lange, M;Grant, PJ
通讯作者：
Grant, PJ
影响因子：
10.4
作者：
De Willige, S. Uitte;De Visser, M. C. H.;Bertina, R. M.
通讯作者：
Bertina, R. M.
影响因子：
8.7
作者：
Colman, RW;White, JV;Sartor, RB
通讯作者：
Sartor, RB