Association of ACE I/D and PAI-1 4G/5G Polymorphisms with Recurrent Pregnancy Loss in the Iranian Population: a Systematic Review and Meta-Analysis

Background: Previous epidemiological studies have reported the relationship of ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss (RPL) in the Iranian population, but the results remained conflicting and controversial. Thus, this study aimed to conduct an updated meta-analysis involving published studies to get a more confidential result.Methods: PubMed, EMBASE, and ISC databases were searched up to February 30, 2019 using the appropriate terms. Odds ratios were pooled using either fixed-effects or random-effects models.Results: A total of 13 studies involving seven studies with 733 cases and 711 controls on ACE I/D polymorphism and six studies with 1155 cases and 699 controls on PAI-1 4G/5G polymorphism were included this meta-analysis. Pooled results showed that there was significant association between ACE I/D polymorphism and RPL in the Iranian population under the allele genetic model (D vs. I: OR = 0.745, 95% CI = 0.641-0.866, P ≤0.001). Moreover, pooled data showed that, there was a significant association between PAI-1 4G/5G polymorphism with RPL risk under all five genetic models i.e., allele (4G4G vs. 5G5G: OR = 2.352, 95% CI = 1.623-3.408, P ≤0.001), heterozygote (4G4G4 vs. 5G5G5: OR = 8.364, 95% CI = 4.744-14.756, P ≤0.001), homozygote (4G5G vs. 5G5G: OR = 2.192, 95% CI = 1.093-4.394, P =0.027), dominate (4G4G4+4G5G vs. 5G5G5: OR = 2.354, 95% CI = 1.309-4.235, P =0.004), and recessive (4G4G4 vs. 4G5G+5G5G5: OR = 5.208, 95% CI = 3.005-9.025, P ≤0.001).Conclusions: Our results indicated that the ACE I/D and PAI-1 4G/5G polymorphisms are correlated with an increased risk of RPL in the Iranian population

Keywords:

Recurrent Pregnancy Loss , Plasminogen activator inhibitor-1 (PAI-1 4G/5G) , Angiotensin-converting enzyme Insertion/Deletion (ACE I/D) , Polymorphism , Meta-Analysis