Genetic Association of Angiotensin-Converting Enzyme (ACE) Gene I/D Polymorphism with Preterm Birth in Korean Women: Case-Control Study and Meta-Analysis

The gene encodes the angiotensin-converting enzyme (ACE), a component of the renin-angiotensin system. Increased ACE activity may cause abnormal regulation of placental circulation and angiogenesis, resulting in adverse pregnancy outcomes. Previous studies have reported that the insertion/deletion (I/D) polymorphism of the gene is associated with the development of preterm birth (PTB). However, results of the association between gene I/D and PTB are inconsistent in various populations. Therefore, we performed a case-control study and a meta-analysis to evaluate the association between I/D polymorphism and PTB. We analyzed a total of 254 subjects (111 patients with PTB and 143 women at ≥38 weeks gestation) for the case-control study. For the meta-analysis, we searched Google Scholar, PubMed, and NCBI databases with the terms "ACE," "angiotensin-converting enzyme," "preterm birth," "preterm delivery," and their combinations. Our results of the case-control study indicated that I/D polymorphism is significantly associated with PTBs in the overdominant genetic model (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.347-0.949, = 0.029) and that the ID genotype of I/D polymorphism has a protective effect for PTB (OR 0.57, 95% CI 0.333-0.986, = 0.043). Similarly, the meta-analysis showed that the OR for the gene ID genotype was 0.66 (95% CI 0.490-0.900, < 0.01). The gene ID genotype has a significant association with PTB and is a protective factor for PTB. A larger sample set and functional studies are required to further elucidate of our findings.