title: Maternal genotype and severe preeclampsia: a HuGE review.
abstract: 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.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Fong
authors.forename: Manpreet K
authors.initials: MK
authors.lastname: Sahemey
authors.forename: Golnessa
authors.initials: G
authors.lastname: Hamedi
authors.forename: Rachel
authors.initials: R
authors.lastname: Eyitayo
authors.forename: Derick
authors.initials: D
authors.lastname: Yates
authors.forename: Valerie
authors.initials: V
authors.lastname: Kuan
authors.forename: Shakila
authors.initials: S
authors.lastname: Thangaratinam
authors.forename: Robert T
authors.initials: RT
authors.lastname: Walton
mesh_terms: D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005838:Genotype; D006801:Humans; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D012307:Risk Factors; D019851:Thrombophilia / Q000235:genetics
keywords: F5 gene; complications; epidemiology; factor V Leiden; genetics; meta-analysis; severe preeclampsia; systematic review; thrombophilia