Association between angiotensin-converting enzyme gene insertion/deletion polymorphism and susceptibility to preterm birth: A case-control study and meta-analysis

Abstract

Background: Preterm birth is the largest contributor to newborn mortality, morbidity, and hospitalization in the first year of life worldwide. Previous studies have suggested the importance of genetic variation in the angiotensin-converting enzyme gene, including the angiotensin-converting enzyme gene insertion/deletion polymorphism, in association with preterm birth. The angiotensin-converting enzyme is a key component of the renin-angiotensin system that is involved in blood pressure homeostasis during pregnancy and also affects risk factors of preterm birth, including the regulation of fibrinolytic system, uteroplacental circulation, vascularization of the placenta, and inflammation.

Objective: The results of previous studies investigating the association between the insertion/deletion polymorphism and susceptibility to preterm birth have been inconsistent, therefore, we have performed a case-control study and conducted a meta-analysis of related studies to clarify this association.

Study design: In a case-control genetic association study, performed on 217 women with a history of preterm birth and 158 women who experienced full-term pregnancy, the significances of associations between allelic and genotype frequencies and preterm birth were determined using Chi-square tests. Following the case-control study, PubMed, Scopus, Google Scholar, and HugeNavigator databases were systematically searched to identify relevant studies. Altogether, four eligible studies involving 369 cases and 559 controls were included in the meta-analysis. The strength of the association between the angiotensin-converting enzyme gene insertion/deletion polymorphism for preterm birth was estimated by odds ratios (ORs) and corresponding 95% confidence intervals (95% CIs), using a fixed-effects model (Mantel-Haenszel method).

Results: In our case-control study we did not detect a significant association of angiotensin-converting enzyme insertion/deletion alleles and genotypes with preterm birth. The results of the meta-analysis showed a significant association between the angiotensin-converting enzyme gene insertion/deletion and the risk of preterm birth under allelic, dominant, and recessive comparison genetic models (D vs. I: OR = 1.35, 95% CI = 1.11-1.65, p = 0.0033; DD + ID vs. II: OR = 1.52, 95% CI = 1.08-2.15, p = 0.0161; DD vs. ID + II: OR = 1.48, 95% CI = 1.07-2.04, p = 0.0184).

Conclusions: The present meta-analysis suggests that the insertion/deletion polymorphism of the angiotensin-converting enzyme gene in mothers might be associated with preterm birth, however, further well-designed large replication studies involving various ethnicities are needed to confirm this association.

Keywords: ACE gene; Case-control association study; Meta-analysis; Preterm birth; Risk factor.