Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: a systematic review and meta-analysis

Background: Many studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of recurrent miscarriage, but the impact is unclear due to inconsistencies among those studies. This study aimed to quantify the strength of the association between ACE I/D polymorphism and recurrent miscarriage risk by performing a systematic review and meta-analysis.

Design and methods: We searched PubMed, Embase, Web of Science, and Wanfang Medicine databases for eligible articles relating the association between ACE I/D polymorphism and risk of recurrent miscarriage in humans. We estimated the summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association.

Results: Eleven studies with a total of 3357 individuals were included in this meta-analysis. Compared to the ACE II genotype, DD and ID were both associated with increased risk of recurrent miscarriage (OR DD versus II=1.81, 95% CI 1.23-2.66, P=0.003; OR ID versus II=1.50, 95% CI 1.25-1.80, P<0.001). Sensitivity analyses further confirmed the association above. No evidence of publication bias was observed.

Conclusion: Meta-analyses of available data show a significant association between ACE I/D polymorphism and recurrent miscarriage risk, and the ACE polymorphic D allele contributes to increased risk of recurrent miscarriage.