A meta-analysis of the association of the ACE I/D and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Iranian women: Are the investigations adequate?

Abstract

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 conducted a meta-analysis to obtain more certain results. A comprehensive literature search was performed in the PubMed, Web of Sciences, Scopus, MedRxiv, SID, and CNKI databases up to January 1st, 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. A total of 14 studies including eight studies with 783 patients and 761 healthy subjects on ACE I/D and six studies with 1.155 patients 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 the number of miscarriages. Our pooled data indicated that ACE I/D and PAI-1 4G/5G polymorphisms were significantly associated with an increased risk of RPL in Iranian women. These significant findings showed that the investigation might be adequate for ACE I/D and PAI-1 4G/5G polymorphisms in the Iranian population.

Association of Fibroblast Growth Factor-1 Promoter Polymorphism and its Serum Concentrations with Repeated Implantation Failure after In vitro Fertilisation: A Cross-sectional Study

“…Decreased FGF-1 expression has been shown in the endometrium of patients with RIF, which is mainly necessary for implantation in the luteal phase. [ 16 ] It has been shown that FGF signalling is important for the maturation and regeneration of endometrium following menstruation. [ 17 ] Changes in the expression of FGF-1 in infertile women have been documented, which shows that FGF-1 is an important maternal factor affecting implantation.…”

Research progress of immune balance and genetic polymorphism in unexplained recurrent abortion

“…A meta-analysis reported that ACE I/D polymorphism had an obvious correlation to RSA, showing that PAI-1 4G/5G had high clinical heterogeneity but did not have an association with RSA [119]. Another metaanalysis concluded that the frequencies of 4G/4G and 4G/5G alleles in RSA patients were higher, which was more obvious in Asian and African groups [120]. Studies also pointed out that ACE I/D and PAI-1 4G/5G polymorphisms were associated with RSA in Iranian and Polish women [121,122].…”