A Meta-Analysis for Association of ACE I/D and PAI-1 4G/5G Polymorphisms with Recurrent Pregnancy Loss in Iranian Women: are the investigations adequate?

¹Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
²Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
³Department of Obstetrics and Gynecology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran
⁴Department of Obstetrics and Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
⁵Mother and Newborn Health Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
⁶Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

Objective: The associations of ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss (RPL) in Iranian women have yielded controversial results. Thus, we carried out a meta-analysis to get more confidential results.
Methods: A comprehensive literature search was carried out in PubMed, Web of Sciences, Scopus, MedRxiv, SID and CNKI databases up to 01 January, 2021 using the appropriate terms. All case-control studies were included. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to estimate the strength of associations.
Results: A total of 14 studies including eight studies with 783 cases and 761 healthy subjects on ACE I/D and six studies with 1,155 cases and 699 healthy subjects on PAI-1 4G/5G were included. Combined data revealed that ACE I/D polymorphism was significantly associated with RPL risk in Iranian women under three models i.e., allele (OR = 0.744, 95% CI: 0.640-0.864, P ≤0.001), dominant (OR = 0.774, 95% CI: 0.601-0.996, P =0.047), and recessive (OR = 0.767, 95% CI: 0.611-0.963, P =0.022). Moreover, the pooled data showed a significant association between the PAI-1 4G/5G polymorphism and RPL risk under all five models i.e., allele (OR = 2.352, 95% CI: 1.623-3.408, P ≤0.001), heterozygote (OR = 8.364, 95% CI: 4.744-14.756, P ≤0.001), homozygote (OR = 2.192, 95% CI: 1.093-4.394, P =0.027), dominant (OR = 2.354, 95% CI: 1.309-4.235, P =0.004), and recessive (OR = 5.208, 95% CI: 3.005-9.025, P ≤0.001). Stratification analysis revealed that these polymorphisms were associated with RPL risk by number of miscarriage.
Conclusions: Our pooled data indicated that ACE I/D and PAI-1 4G/5G polymorphisms are significantly associated with an increased risk of RPL in Iranian women. These significant findings brought us to the decision that the investigation might be adequate for ACE I/D and PAI-1 4G/5G polymorphisms in the Iranian population.

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Seyed Alireza Dastgheib, Mojgan Karimi-Zarchi, Reza Bahrami, Razie Sadat Tabatabaei, Atiyeh Javaheri, Mahmood Noorishadkam, Seyed Reza Mirjalili, Hossein Neamatzadeh. A Meta-Analysis for Association of ACE I/D and PAI-1 4G/5G Polymorphisms with Recurrent Pregnancy Loss in Iranian Women: are the investigations adequate?. . 2021; 18(2): 0-0

Corresponding Author: Reza Bahrami, Iran