title: Genetic variants in pre-eclampsia: a meta-analysis.
abstract: BACKGROUND Pre-eclampsia has a clear familial component, suggesting that the condition may be partly attributable to genetic susceptibility. The search for susceptibility genes has led to a drastic increase in the number of published studies associating genetic factors with pre-eclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis assessed the pooled effect of each genetic variant that is reproducibly associated with pre-eclampsia. METHODS Studies that assessed the association between genes and pre-eclampsia were searched in PubMed, Embase and Web of Science. We selected all genetic variants that were significantly associated with pre-eclampsia in an initial study and were subsequently independently reproduced in at least one additional study. All studies that assessed these reproduced variants were then included. The association between genetic variants and pre-eclampsia was calculated at the allele level, and the main measure of effect was a pooled odds ratio in a random-effects model. RESULTS The literature search yielded 2965 articles, of which 542 investigated genetic associations in pre-eclampsia. We identified 22 replicated genetic variants, of which 7 remained significantly associated with pre-eclampsia following meta-analysis. These variants were in or near the following genes: ACE, CTLA4, F2, FV, LPL and SERPINE1. CONCLUSIONS This meta-analysis identified seven genetic variants associated with pre-eclampsia. Importantly, many of these variants are also risk factors for developing cardiovascular disease, revealing that pre-eclampsia and cardiovascular disease have shared genetic risk factors. The contribution of the identified genetic variants in the pathogenesis of pre-eclampsia should be the focus of future studies.
authors.affiliation: Department of Pathology, Leiden University Medical Center, Leiden, the Netherlands. a.j.buurma@lumc.nl
authors.forename: A J
authors.initials: AJ
authors.lastname: Buurma
authors.forename: R J
authors.initials: RJ
authors.lastname: Turner
authors.forename: J H M
authors.initials: JH
authors.lastname: Driessen
authors.forename: A L
authors.initials: AL
authors.lastname: Mooyaart
authors.forename: J W
authors.initials: JW
authors.lastname: Schoones
authors.forename: J A
authors.initials: JA
authors.lastname: Bruijn
authors.forename: K W M
authors.initials: KW
authors.lastname: Bloemenkamp
authors.forename: O M
authors.initials: OM
authors.lastname: Dekkers
authors.forename: H J
authors.initials: HJ
authors.lastname: Baelde
mesh_terms: D000483:Alleles; D060908:CTLA-4 Antigen; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics; D011225:Pre-Eclampsia / Q000235:genetics*; D011247:Pregnancy; D012307:Risk Factors
chemical_list: D060908:CTLA-4 Antigen; D017395:Plasminogen Activator Inhibitor 1