Genetic Thrombophilias and Preeclampsia: A Meta-Analysis

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Abstract
To assess the relationship between the factor V Leiden (1691 G-A) single nucleotide polymorphism (SNP), the methylene tetrahydrofolate reductase (MTHFR) 677 C-T SNP, and the prothrombin 20210 G-A SNP and the risk of preeclampsia, by conducting a meta-analysis of all case-control studies with data on these polymorphisms and the risk of preeclampsia. MEDLINE (1966 to November 2002), EMBASE (1980 to November 2002). Search terms included "preeclampsia," "thrombophilia," "factor V Leiden," "protein C," "MTHFR," "methylenetetrahydrofolate reductase," "homocysteine," and "prothrombin gene 20210." Case-control studies of genetic thrombophilias and preeclampsia were included. We identified 349 titles and reviewed 47 articles for inclusion and exclusion criteria. Thirty-one studies with 7,522 patients were included in the meta-analysis. Data from patients characterized as having severe preeclampsia were extracted and analyzed separately. The pooled odds ratio (OR) for the association of factor V Leiden and all cases of preeclampsia was 1.81 (95% confidence interval [CI] 1.14-2.87) and 2.24 (95% CI 1.28-3.94) for cases of severe preeclampsia. The pooled OR for the MTHFR 677 TT genotype and all preeclampsia was 1.01 (95% CI 0.79-1.29) and 1.38 (95% CI 0.93-2.06) for severe preeclampsia. The OR for the prothrombin 20210 polymorphism and all preeclampsia was 1.37 (95% CI 0.72-2.57) and 1.98 (.94-4.17) for severe preeclampsia. This meta-analysis suggests that the factor V Leiden SNP is associated with an increased risk of preeclampsia. Further studies are warranted to determine whether subgroups of high-risk women should be screened for this mutation.