Homocysteine, MTHFR and risk of venous thrombosis:: a meta-analysis of published epidemiological studies

被引:335
作者
Den Heijer, M
Lewington, S
Clarke, R
机构
[1] Univ Nijmegen, Radboud Med Ctr, Dept Endocrinol 531, NL-6500 HB Nijmegen, Netherlands
[2] Univ Oxford, Radcliffe Infirm, Clin Trial Serv Unit, Oxford OX2 6HE, England
[3] Univ Oxford, Radcliffe Infirm, Epidemiol Studies Unit, Oxford OX2 6HE, England
关键词
homocysteine; MTHFR; venous thrombosis;
D O I
10.1111/j.1538-7836.2005.01141.x
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context: It has been suggested that elevated total plasma homocysteine levels are associated with the risk of venous thrombosis. Objective: To assess the relationship of homocysteine and the MTHFR 677TT genotype and the risk of venous thrombosis by conducting a meta-analysis of all relevant studies. Data sources and selection: Studies (case-control or nested case-control) were identified by searches of electronic literature for relevant reports published before July 2003 on homocysteine and the MTHFR 677TT genotype and venous thrombosis as an end-point, by hand-searching reference lists of original articles (including meta-analyses) on this topic and by contact with investigators in the field. Data extraction: A meta-analysis of 24 retrospective (n = 3289 cases) and three prospective studies (n = 476 cases) was carried out to examine the association of homocysteine with venous thrombosis. A meta-analysis of 53 studies (n = 8364 cases) of the MTHFR 677TT genotype (that increases homocysteine) was carried out to assess if this association is causal. Data synthesis: A 5 mumol L-1 higher measured homocysteine level was associated with a 27% (95% Cl: 1-59) higher risk of venous thrombosis in prospective studies and a 60% (95% CI: 10-134) higher risk in retrospective studies. The 677TT genotype was associated with a 20% (95% CI: 8-32) higher risk of venous thrombosis compared with the 677CC genotype. In contrast with non-American studies, the 677TT genotype had no effect on venous thrombosis in North America, due probably to the higher intake of folate and riboflavin in North America. Conclusion: This meta-analysis of prospective and retrospective studies demonstrates a modest association of homocysteine with venous thrombosis. The elevated risk associated with the MTHFR 677TT genotype provides some support for causality.
引用
收藏
页码:292 / 299
页数:8
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