Association of Angiotensin-Converting Enzyme Insertion/Deletion Polymorphism with Recurrent Pregnancy Loss: a Meta-Analysis of 26 Case-Control Studies.

Elnaz Foroughi,Fereshteh Aslbahar,Hossein Neamatzadeh,Rezvan Nasiri,Razieh Sadat Tabatabaiee,Mojgan Karimi-Zarchi,Mahta Mazaheri,Atiyeh Javaheri

doi:10.1055/s-0038-1672137

Abstract

Previous studies investigating the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and recurrent pregnancy loss (RPL) risk has provided inconsistent results. The aim of our study was to assess the association between the ACE I/D polymorphism and risk of RPL. All studies published up to January 30, 2018 on the association of ACE I/D polymorphism with RPL were identified by searching the PubMed, Web of Knowledge, and Google scholar databases. A total of 26 case-control studies with 3,140 RPL cases and 3,370 controls were included in the meta-analysis. Overall, there was a significant association between ACE I/D polymorphism and RPL risk under the allele model (I versus D: odds ratio [OR] = 0.538, 95% confidence interval [CI] = 0.451-0.643, p ≤ 0.001), the homozygote model (II versus DD: OR = 0.766, 95% CI = 0.598-0.981, p = 0.035) and the recessive model (II versus ID + DD: OR = 0.809, 95% CI = 0.658-0.994, p = 0.044). Subgroup analysis by ethnicity showed that there was a significant association between ACE I/D polymorphism and increased risk of RPL in Caucasian and West-Asian populations, but not in East-Asians. When stratified by number of recurrent miscarriages (RMs), a significant association between ACE I/D polymorphism and increased risk of RPL was detected in the group of studies with ≥ 2 RMs, but not in studies with ≥ 3 RMs. The meta-analysis suggests that ACE I/D polymorphism is associated with increased risk of RPL. The ACE I/D polymorphism may be a risk factor for RPL in Caucasian and West-Asian populations, but not in East-Asians.

Highlights

Recurrent pregnancy loss (RPL) is a surprisingly common occurrence, which traditionally is defined as 3 or more (! 3) consecutive miscarriages before 20 weeks of pregnancy.[1,2] this definition is not used consistently, and pregnancy losses at higher gestational ages are in some literatures, classified as miscarriage instead of stillbirth or preterm neonatal death.[3]
There was a significant association between angiotensin-converting enzyme (ACE) I/D polymorphism and RPL risk under the allele model (I versus D: odds ratio [odds ratios (ORs)] 1⁄4 0.538, 95% confidence interval [confidence intervals (CIs)] 1⁄4 0.451–0.643, p 0.001), the homozygote model (II versus DD: OR 1⁄4 0.766, 95% CI 1⁄4 0.598–0.981, p 1⁄4 0.035) and the recessive model (II versus ID þ DD: OR 1⁄4 0.809, 95% CI 1⁄4 0.658–0.994, p 1⁄4 0.044)
The meta-analysis suggests that ACE I/D polymorphism is associated with increased risk of RPL

Summary

Introduction

Recurrent pregnancy loss (RPL) is a surprisingly common occurrence, which traditionally is defined as 3 or more (! 3) consecutive miscarriages before 20 weeks of pregnancy.[1,2] this definition is not used consistently, and pregnancy losses at higher gestational ages are in some literatures, classified as miscarriage instead of stillbirth or preterm neonatal death.[3]. More than 30 putative major genes involved in immunity (PP14, Annexin II, PIBF, and HLA-DRB1) and angiogenesis (TGF-β, VEGF, TIMP-1, MMP-2, MMP-9, ACE) genes for RPL have been identified.[9,10,11]

Methods

Results

Conclusion