title: Common genetic risk factors for venous thrombosis in the Chinese population.
abstract: Venous thrombosis is a major medical disorder caused by both genetic and environmental factors. Little is known about the genetic background of venous thrombosis in the Chinese population. A total of 1,304 individuals diagnosed with a first venous thrombosis and 1,334 age- and sex-matched healthy participants were enrolled in this study. Resequencing of THBD (encoding thrombomodulin) in 60 individuals with venous thrombosis and 60 controls and a functional assay showed that a common variant, c.-151G>T (rs16984852), in the 5' UTR significantly reduced the gene expression and could cause a predisposition to venous thrombosis. Therefore, this variant was genotyped in a case-control study, and results indicated that heterozygotes had a 2.80-fold (95% confidence interval = 1.88-4.29) increased risk of venous thrombosis. The THBD c.-151G>T variant was further investigated in a family analysis involving 176 first-degree relatives from 38 index families. First-degree relatives with this variant had a 3.42-fold increased risk of venous thrombosis, and their probability of remaining thrombosis-free was significantly lower than that of relatives without the variant. In addition, five rare mutations that might be deleterious were also identified in thrombophilic individuals by sequencing. This study is the largest genetic investigation of venous thrombosis in the Chinese population. Further study on genetics of thrombosis should focus on resequencing of THBD and other hemostasis genes in different populations.
authors: Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors: Liang
authors: L
authors: Tang
authors: Hua-Fang
authors: HF
authors: Wang
authors: Xuan
authors: X
authors: Lu
authors: Xiao-Rong
authors: XR
authors: Jian
authors: Bi
authors: B
authors: Jin
authors: Hong
authors: H
authors: Zheng
authors: Yi-Qing
authors: YQ
authors: Li
authors: Qing-Yun
authors: QY
authors: Wang
authors: Tang-Chun
authors: TC
authors: Wu
authors: Huan
authors: H
authors: Guo
authors: Hui
authors: H
authors: Liu
authors: Tao
authors: T
authors: Guo
authors: Jian-Ming
authors: JM
authors: Yu
authors: Rui
authors: R
authors: Yang
authors: Yan
authors: Y
authors: Yang
authors: Yu
authors: Y
authors: Hu
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D002681:China; D018572:Disease-Free Survival; D005190:Family; D005260:Female; D005786:Gene Expression Regulation; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D012307:Risk Factors; D012995:Solubility; D018180:Thrombomodulin / Q000235:genetics; D020246:Venous Thrombosis / Q000235:genetics*
chemical_list: D018180:Thrombomodulin