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J Thromb Haemost. 2005 Feb;3(2):292-9.

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

Author information

  • 1Department of Endocrinology (531), Radboud University Nijmegen Medical Centre, PO Box 9101, 6500 HB Nijmegen, the Netherlands. m.denheijer@endo.umcn.nl

Abstract

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 micromol L(-1) higher measured homocysteine level was associated with a 27% (95% CI: 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.

PMID:
15670035
[PubMed - indexed for MEDLINE]
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