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

Abstract

Background and Objectives: The ACE 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 ACE gene is associated with the development of preterm birth (PTB). However, results of the association between ACE 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 ACE I/D polymorphism and PTB. Materials and Methods: 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. Results: Our results of the case-control study indicated that ACE 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, p = 0.029) and that the ID genotype of ACE I/D polymorphism has a protective effect for PTB (OR 0.57, 95% CI 0.333–0.986, p = 0.043). Similarly, the meta-analysis showed that the OR for the ACE gene ID genotype was 0.66 (95% CI 0.490–0.900, p < 0.01). Conclusion: The ACE 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.

The association of angiotensin-converting enzyme gene polymorphism with respiratory distress syndrome in premature neonates

“…25 In the current study, multivariate analysis showed birth weight, birth length, and head circumference did not interfere with the difference in the ACE gene polymorphism between the case and control group except for the gestational age, which was proposed by other studies to be associated with ACE gene polymorphism. 26,27 We concluded that in premature neonates, D/D genotype and D-alleles are protective factors from RDS. I/I genotype and I-alleles are associated with more severity and complications of RDS.…”

The Angiotensin-converting Enzyme Insertion/Deletion Polymorphism as a Common Risk Factor for Major Pregnancy Complications

“…A meta-analysis of 4 studies including 928 individuals (369 PTB cases and 559 controls) has revealed a significant association between ACE D allele carrier status and risk for PTB in various populations (58). On the contrary, another study in Korean women (111 PTB cases and 143 controls) have not observed such an association (62).…”

“…PTB is caused by various factors, including abnormal placentation, inflammatory conditions, gestational bleeding, cervical and uterine abnormalities, as well as genetic factors (61,62). PTB has also been associated with blood pressure dysregulation during pregnancy, involving RAS and ACE in particular, while some studies have specifically suggested involvement of the ACE I/D polymorphism (58,61,62).…”

Association of Angiotensin-I-Converting Enzyme (ACE) Insertion/ Deletion Gene Polymorphism with Preeclampsia Susceptibility in Egyptian women

“…An insertion-deletion (I/D) of the 287-bp Alu repetitive region in intron 16 of the gene is one of these polymorphisms. The polymorphism has little effect on protein structure; however, it does appear to affect gene expression (Lee et al 2019).…”