A meta-analysis for association of eNOS VNTR 4b/a, - 786 T > C and + 894G > T polymorphisms with risk of recurrent pregnancy loss

Abstract

Background: The association of polymorphisms at nitric oxide synthases (eNOS) gene with recurrent pregnancy loss (RPL) susceptibility has been the focus of attention in several studies. However, the conclusions have been divergent and controversial. Therefore, we performed this study to precisely evaluate the association of eNOS polymorphisms with the risk of RPL.

Methods: A universal search in PubMed, Web of Knowledge, SciELO, MedRxiv, Scopus and web of Science was performed to identify relevant studies up to January 25, 2020.

Results: A total of 39 eligible studies including 15 studies with 2274 cases and 1933 controls on VNTR 4b/a, nine studies with 1640 cases and 1268 controls on -786C > T, and 15 studies with 2660 cases and 2557 controls on + 894G > T polymorphism were selected. Pooled data revealed that eNOS VNTR 4b/a (dominant model: OR = 1.174, 95% CI 1.021-1.350, p = 0.025) and + 894G > T (allele model: OR = 1.278, 95% CI 1.024-1.595, p = 0.030; homozygote model: OR = 1.442, 95% CI 1.084-1.917, p = 0.012; dominant model: OR = 1.305, 95% CI 1.006-1.693, p = 0.045; and recessive model: OR = 1.378, 95% CI 1.045-1.817, p = 0.023) polymorphisms were significantly associated with an increased risk of RPL, but not - 786 T > C. Stratified analysis by ethnicity revealed that the eNOS + 894G > T was associated with RPL risk in Asians.

Conclusions: To sum up, our results indicated that the eNOS VNTR 4b/a and + 894G > T polymorphisms might be contributing to RPL development, but not the - 786C > T polymorphism.

Keywords: Miscarriage; Nitric oxide; Polymorphism; Recurrent pregnancy loss; eNOS.