Maternal genotype and severe preeclampsia: a HuGE review.
335 - 345
Am J Epidemiol
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Severe preeclampsia is a common cause of maternal and perinatal morbidity worldwide. The disease clusters in families; however, individual genetic studies have produced inconsistent results. We conducted a review to examine relationships between maternal genotype and severe preeclampsia. We searched the MEDLINE and Embase databases for prospective and retrospective cohort and case-control studies reporting associations between genes and severe preeclampsia. Four reviewers independently undertook study selection, quality assessment, and data extraction. We performed random-effects meta-analyses by genotype and predefined functional gene group (thrombophilic, vasoactive, metabolic, immune, and cell signalling). Fifty-seven studies evaluated 50 genotypes in 5,049 cases and 16,989 controls. Meta-analysis showed a higher risk of severe preeclampsia with coagulation factor V gene (proaccelerin, labile factor) (F5) polymorphism rs6025 (odds ratio = 1.90, 95% confidence interval: 1.42, 2.54; 23 studies, I(2) = 29%), coagulation factor II (thrombin) gene (F2) mutation G20210A (rs1799963) (odds ratio = 2.01, 95% confidence interval: 1.14, 3.55, 9 studies, I(2) = 0%), leptin receptor gene (LEPR) polymorphism rs1137100 (odds ratio = 1.75, 95% confidence interval: 1.15, 2.65; 2 studies, I(2) = 0%), and the thrombophilic gene group (odds ratio = 1.87, 95% confidence interval: 1.43, 2.45, I(2) = 27%). There were no associations with other gene groups. There was moderate heterogeneity between studies and potential for bias from poor-quality genotyping and inconsistent definition of phenotype. Further studies with robust methods should investigate genetic factors that might potentially be used to stratify pregnancies according to risk of complications.
AuthorsFong, FM; Sahemey, MK; Hamedi, G; Eyitayo, R; Yates, D; Kuan, V; Thangaratinam, S; Walton, RT
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