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

Mol Hum Reprod. 2013 Mar;19(3):136-43. doi: 10.1093/molehr/gas056. Epub 2012 Nov 23.

Abstract

The SERPINE1 -675 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 I(2) 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 -675 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 (I(2) = 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 -675 4G/5G and PE. Meta-analysis results support this polymorphism as a likely susceptibility variant for PE.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Alleles
  • Female
  • Genes, Recessive
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Humans
  • Mutagenesis, Insertional*
  • Odds Ratio
  • Plasminogen Activator Inhibitor 1 / genetics*
  • Pre-Eclampsia / genetics*
  • Pre-Eclampsia / pathology
  • Pregnancy
  • Promoter Regions, Genetic
  • Sequence Deletion*

Substances

  • Plasminogen Activator Inhibitor 1