OS050. Genetic variants in pre-eclampsia: a meta-analysis

• Published in: Pregnancy hypertension Vol. 2; no. 3; p. 204
• Main Authors: Buurma, A, Turner, R, Driessen, A, Mooyaart, A, Schoones, J, Bruijn, J.A, Bloemenkamp, K, Baelde, H
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2012
• Subjects: Cardiovascular; Obstetrics and Gynecology
• ISSN: 2210-7789; 2210-7797
• DOI: 10.1016/j.preghy.2012.04.051

Introduction Preeclampsia has a clear familial component, suggesting that the syndrome may be partly attributable to genetic susceptibility. The search for susceptibility genes has lead to a massive increase in the number of published studies involving genetic associations in preeclampsia. However, attempts to replicate these findings have yielded inconsistent results. This meta-analysis aims to assess the pooled effect of each genetic variant that is reproducibly associated with preeclampsia. Objectives To create an overview of the genetic variants that are reproducibly associated with preeclampsia. Methods Studies assessing the association between genes and preeclampsia were searched in PubMed, EMBASE and Web of Science. We selected all genetic variants that were significantly associated with preeclampsia in an initial study and then independently reproduced in at least one additional study. Subsequently, all studies assessing these reproduced variants were included. The association between these variants and preeclampsia was calculated at the allele level and the main measure of effect was a pooled odds ratio. Results The literature search resulted in 2965 citations, of which 542 were genetic association studies investigating preeclampsia. We identified 23 replicated genetic variants, of which 8 remained significantly associated with preeclampsia in a random-effects meta-analysis. These variants were in or near the following genes: ACE , AGT , CTLA4 , F2 , FV (two variants), LPL and SERPINE1. Conclusion This meta-analysis found 8 genetic variants associated with preeclampsia. Most of these variants are in the renin-angiotensin and the coagulation system. Importantly, many of the variants that were associated with preeclampsia are known to be risk factors for the development of cardiovascular disease, indicating that preeclampsia and cardiovascular disease have shared genetic risk factors. The relative contribution and relevance of the identified genes in the pathogenesis of preeclampsia should be the focus of future studies.