Evaluation of iNOS -2087A>G polymorphism in recurrent pregnancy loss

Abstract

Background: Due to its role in angiogenesis, the inducible nitric oxide synthase (iNOS) gene promoter polymorphism may have a presumed role in recurrent spontaneous abortions (RSA). It is an intensely studied protein, a biological mediator, a modulator and an effector molecule by implication in numerous physiological processes: vasodilatation, angiogenesis, immunity, tissue remodeling, smooth muscle activity.

Aim: Our study aims to investigate a possible association between iNOS -2087A>G (rs2297518) polymorphism and the occurrence of idiopathic recurrent pregnancy loss (RPL).

Patients, materials and methods: In this study, as in the previously published one, 169 women, diagnosed with RPL, in the Clinics of Obstetrics and Gynecology, "Filantropia" Municipal Hospital, Craiova, Romania, were subjected to the analysis, from October 2009 to October 2016. As a control group, we used 145 women. Subjects from both groups were genotyped using specific probes for TaqMan polymerase chain reaction (PCR), allelic discrimination technique.

Results: We evaluated in this study a possible association between iNOS -2087A>G (rs2297518) polymorphism and the occurrence of idiopathic RPL. The chi-square test showed no significant association between the presence of this polymorphism and the increased risk to develop RPL. When we performed a comparative analysis of the frequency of genotypes and our statistical data, it was observed that this polymorphism, iNOS -2087A>G (rs2297518), has not been associated with an increased risk of developing RPL. Also, when one genotype was compared with another, we did not obtain any association that would have statistical significance, between the presence of this polymorphism and the increased risk for patients to develop RPL [in dominant - A allele carriers, iNOS 2087 AG+AA vs. GG: odds ratio (OR) 1.31, 95% confidence interval (CI) 0.83-2.07, p=0.24]. Analyzing the overall risk of developing RPL by iNOS 2087 single-nucleotide polymorphism (SNP) genotype frequencies, between controls and RPL patients (which were stratified by number of consecutive PLs), taking into account the number of consecutive pregnancies, the chi-square test showed no association between the presence of this polymorphism and the increased risk for developing RPL in all three subgroups we analyzed (in a dominant model - A allele carriers, iNOS 2087 AG+AA vs. GG: the first subgroup, OR 1.31, 95% CI 0.83-2.07, p=0.24; the second subgroup, OR 1.26, 95% CI 0.76-2.11, p=0.37; the three subgroup, OR 1.4, 95% CI 0.77-2.53, p=0.272).

Conclusions: The iNOS -2087A>G (rs2297518) gene polymorphism does not influence RPL in the study area of Dolj County, Romania.