Department of Genetics, Marvdasht Branch, Azad University, Marvdasht, Iran.
Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Arch Gynecol Obstet. 2021 Nov;304(5):1135-1151. doi: 10.1007/s00404-021-06172-x. Epub 2021 Aug 13.
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.
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.
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.
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.
一氧化氮合酶（eNOS）基因多态性与复发性妊娠丢失（RPL）易感性的关联一直是多项研究的关注焦点。然而，结论却存在分歧和争议。因此，我们进行了这项研究，以精确评估 eNOS 多态性与 RPL 风险的关联。
我们在 PubMed、Web of Knowledge、SciELO、MedRxiv、Scopus 和 Web of Science 上进行了全面检索，以查找截至 2020 年 1 月 25 日的相关研究。
共纳入 39 项符合条件的研究，其中 15 项研究涉及 VNTR 4b/a 的 2274 例病例和 1933 例对照，9 项研究涉及-786C>T 的 1640 例病例和 1268 例对照，15 项研究涉及+894G>T 多态性的 2660 例病例和 2557 例对照。汇总数据显示，eNOS VNTR 4b/a（显性模型：OR=1.174，95%CI 1.021-1.350，p=0.025）和+894G>T（等位基因模型：OR=1.278，95%CI 1.024-1.595，p=0.030；纯合子模型：OR=1.442，95%CI 1.084-1.917，p=0.012；显性模型：OR=1.305，95%CI 1.006-1.693，p=0.045；和隐性模型：OR=1.378，95%CI 1.045-1.817，p=0.023）多态性与 RPL 风险增加显著相关，但-786T>C 多态性则不然。按种族进行分层分析显示，eNOS+894G>T 与亚洲人群的 RPL 风险相关。
总之，我们的研究结果表明，eNOS VNTR 4b/a 和+894G>T 多态性可能与 RPL 的发生有关，但-786C>T 多态性则不然。
