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

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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.

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Availability of data and material

The datasets generated during and/or analyzed during this study are the corresponding author on reasonable request.

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Acknowledgements

The authors thank the editors and the anonymous reviewers for their insightful suggestions on this study.

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Authors and Affiliations

  1. Department of Genetics, Marvdasht Branch, Azad University, Marvdasht, Iran

    Hossein Golestanpour

  2. Biotechnology Research Center, International Campus, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Hossein Golestanpour

  3. Neonatal Research Center, Shiraz University of Medical Sciences, Shiraz, Iran

    Reza Bahrami

  4. Department of Medical Genetics, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran

    Seyed Alireza Dastgheib

  5. Department of Obstetrics and Gynecology, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Razieh Sadat Tabatabaei & Atiyeh Javaheri

  6. Mother and Newborn Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Razieh Sadat Tabatabaei, Atiyeh Javaheri, Seyed Reza Mirjalili & Hossein Neamatzadeh

  7. Department of Obstetrics and Gynecology, Firoozgar Hospital, Iran University of Medical Sciences, Tehran, Iran

    Mojgan Karimi-Zarchi

  8. Endometriosis Research Center, Iran University of Medical Sciences, Tehran, Iran

    Mojgan Karimi-Zarchi

  9. Department of Medical Genetics, Shahid Sadoughi University of Medical Sciences, Yazd, Iran

    Hossein Neamatzadeh

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  1. Hossein Golestanpour
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Contributions

HG, SAD, RB: conceptualization; SAD, HN: software, investigation, writing, original draft preparation; SRM, RST, AJ: investigation; SAD, HG: investigation, writing; SAD, HN, MKZ1: methodology, software; HN, HG: formal analysis, investigation and SAD, RB, HN: writing, reviewing, editing.

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Correspondence to Seyed Alireza Dastgheib.

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Golestanpour, H., Bahrami, R., Dastgheib, S.A. et al. A meta-analysis for association of eNOS VNTR 4b/a,  – 786 T > C and + 894G > T polymorphisms with risk of recurrent pregnancy loss. Arch Gynecol Obstet 304, 1135–1151 (2021). https://doi.org/10.1007/s00404-021-06172-x

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