Genetic Thrombophilias and Preeclampsia: A Meta-Analysis : Obstetrics & Gynecology (original) (raw)

Review

From the *Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and †Weill Medical College of Cornell University, New York, New York.

Address reprint requests to: Phyllis August, MD, MPH, Weill Medical College of Cornell University, 525 East 68th Street, New York, New York 10021; e-mail: [email protected].

Received April 12, 2004. Received in revised form July 27, 2004. Accepted August 5, 2004.

OBJECTIVE:

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.

DATA SOURCES:

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.”

METHODS OF STUDY SELECTION:

Case-control studies of genetic thrombophilias and preeclampsia were included.

TABULATION, INTEGRATION, AND RESULTS:

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.

CONCLUSION:

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.