Excessive generation of plasminogen activator inhibitor-type 1 (PAI-1) is implicated in the pathogenesis of pre-eclampsia. The PAI-1 (-675 4G/5G) promoter polymorphism (rs1799889) affects transcriptional activity and is a putative risk factor for pre-eclampsia. The aim of this study was to identify, appraise and synthesise the available evidence for the association of the PAI-1 (-675 4G/5G) polymorphism with pre-eclampsia.
Searches
MEDLINE and EMBASE (1996- September 2012) via OVID using these terms:
1. [pregnan* AND (blood press* OR hypertens*)] OR PIH OR pre-eclampsia OR eclampsia OR pregnancy induced hypertension OR HELLP syndrome
AND
2. [Plasminogen Activator Inhibitor 1 OR PAI OR SERPINE] AND polymorphism.
US National Institutes of Health-sponsored Genetic Associations Database (http://geneticassociationdb.nih.gov) and the reference lists of all potentially eligible articles.
Types of study to be included
Case-control and cohort studies that assessed the association of the PAI-1 (-675 4G/5G) polymorphism with pre-eclampsia.
Condition or domain being studied
Pre-eclampsia: hypertension and proteinuria in pregnancy. Affects ~5% pregnant women, major cause maternal and fetal morbidity and mortality. Aetio-pathogenesis not understood.
Participants/ population
Case-control and cohort studies that assessed the association of the PAI-1 (-675 4G/5G) polymorphism with pre-eclampsia.
Intervention(s), exposure(s)
Polymorphism of the plasminogen activator inhibitor-type 1 (PAI-1) gene.
Comparator(s)/ control
Comparator polymorphism.
Context
(1) Pre-eclampsia defined as per international consensus criteria as systolic blood pressure >140 mm Hg or diastolic blood pressure >90 mm Hg occurring after 20 weeks’ gestation in a woman whose blood pressure has previously been normal accompanied by proteinuria of >300 mg per 24 h or =”2+” by semi-quantitive near-patient testing (“dipstick”). Studies that included women with eclampsia or HELLP syndrome (microangiopathic haemolysis, thrombocytopaenia, and elevated liver enzymes) included.
(2) Control group consists of women without a history of pre-eclampsia in pregnancy. Studies using controls recruited from a general population (for example, blood donors) excluded.
(3) Cases and controls matched for ethnic group or study reports the ethnic ancestry of participants to allow for stratified analysis.
(4) Genotype distribution within the controls consistent with Hardy-Weinberg equilibrium assessed using Pearson’s chi-squared analysis.
Outcome(s)
Primary outcomes
Association of PAI-1) -675 (4G/5G) polymorphism with pre-eclampsia.
Secondary outcomes
Measures of heterogeneity, funnel plot asymmetry, publication or small-study bias.
Data extraction, (selection and coding)
Two authors independently use a standardised reporting form to abstract information on setting, design, and inclusion criteria from each potentially eligible study. Contact study investigators to obtain additional information if necessary.
Risk of bias (quality) assessment
Assessment of case-definition, control matching, population stratification, and genotype blinding.
Strategy for data synthesis
Meta-analysis of genotype-phenotype association by inverse variance-weighted method in a random effects model to calculate the summary odds ratio and 95% confidence interval.
Analysis of subgroups or subsets
Study size (to examine for small study bias).
Dissemination plans
Publication in peer-reviewed journal.
Contact details for further information
William McGuire
Centre for Reviews and Dissemination
University of York
YO10 5DD UK
william.mcguire@hyms.ac.uk
Organisational affiliation of the review
NIHR Centre for Reviews and Dissemination
http://www.crd.york.ac.uk/
Review team
Professor William McGuire, Centre for Reviews and Dissemination Dr Jessie Morgan, Centre for Reviews and Dissemination
Formal screening of search results against eligibility criteria
Data extraction
Risk of bias (quality) assessment
Data analysis
Prospective meta-analysis
PROSPERO This information has been provided by the named contact for this review. CRD has accepted this information in good faith and registered the review in PROSPERO. CRD bears no responsibility or liability for the content of this registration record, any associated files or external websites.
