title: 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 -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.
authors.affiliation: Center for Perinatal, Pediatric and Environmental Epidemiology, Yale Schools of Public Health and Medicine, New Haven, CT 06510, USA. linlu.zhao@yale.edu
authors.forename: Linlu
authors.initials: L
authors.lastname: Zhao
authors.forename: Michael B
authors.initials: MB
authors.lastname: Bracken
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Dewan
authors.forename: Suzan
authors.initials: S
authors.lastname: Chen
mesh_terms: D000483:Alleles; D005260:Female; D005808:Genes, Recessive; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016254:Mutagenesis, Insertional; D016017:Odds Ratio; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011225:Pre-Eclampsia / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D017384:Sequence Deletion
chemical_list: D017395:Plasminogen Activator Inhibitor 1