Background Plasma levels of plasminogen activator inhibitor-type 1 (PAI-1) are higher in women with severe pre-eclampsia/eclampsia (PE/E) than in gestation-matched non-hypertensive pregnant women. The PAI-1 (−675 4G) promoter polymorphism increases transcriptional activity and is a putative risk factor for PE/E. The aim of this study was synthesise the available evidence for the association of the PAI-1 (−675 4G) polymorphism with PE/E.

Methods Systematic review and random effects meta-analysis of genetic association studies using HuGE review methods.

Results 11 case-control studies in which a total of 1331 women with PE/E and 1536 controls participated were identified. The studies were generally small but of reasonable methodological quality. Random effects meta-analysis found a significant association: pooled odds ratio 1.36 (95% CI 1.13 to 1.63). (Figure 1). There was not any statistical evidence of heterogeneity (I²=0%).

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Abstract PMM.12 Figure 1

Forest plot of odds of PAI-1 (−675 4G/4G) in PE/E versus controls.

Conclusions This meta-analysis suggests that women with PE/E have a 36% increased odds of possession of the PAI-1 (−675 4G/4G) polymorphism. These findings if confirmed in a larger genetic association studies may have implications for both clinical care (targeted surveillance or prophylaxis) and future research to define the pathogenesis of this condition.