Association between the SERPINE1 (PAI-1) 4G/5G insertion/deletion promoter polymorphism (rs1799889) and pre-eclampsia: A systematic review and meta-analysis

Abstract

The SERPINE1 2675 4G/5G promoter region insertion/deletion polymorphism (rs1799889) has been implicated in the pathogenesis of pre-eclampsia (PE), but the genetic association has been inconsistently replicated. To derive a more precise estimate of the association, a systematic review and meta-analysis was conducted. This study conformed to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed (MEDLINE), Scopus and HuGE Literature Finder literature databases were systematically searched for relevant studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the allelic comparison (4G versus 5G) and genotypic comparisons following the co-dominant (4G/4G versus 5G/5G and 4G/5G versus 5G/5G), dominant (4G/4G+4G/5G versus 5G/5G) and recessive (4G/4G versus 4G/5G+5G/5G) genetic models. Between-study heterogeneity was quantified by I2 statistics and publication bias was appraised with funnel plots. Sensitivity analysis was conducted to evaluate the robustness of meta-analysis findings. Meta-analysis of 11 studies involving 1297 PE cases and 1791 controls found a significant association between the SERPINE1 2675 4G/5G polymorphism and PE for the recessive genetic model (OR=1.36, 95% CI: 1.13-1.64, P=0.001), a robust finding according to sensitivity analysis. A low level of between-study heterogeneity was detected (I2=20%) in this comparison, which may be explained by ethnic differences. Funnel plot inspection did not reveal evidence of publication bias. In conclusion, this study provides a comprehensive examination of the available literature on the association between SERPINE1 2675 4G/5G and PE. Meta-analysis results support this polymorphism as a likely susceptibility variant for PE. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.