Association of endothelial nitric oxide synthase gene variants in pre-eclampsia: an updated systematic review and meta-analysis

Abstract

Introduction

Three common endothelial nitric oxide synthase (eNOS) gene variants are existed such as; G-894T, T-786C, and variable number tandem repeats in intron-4 (VNTR intron-4) which has been proposed to be linked with PE. However, there is still debate regarding the findings. To address this, a review was conducted to assess the potential association of eNOS gene variants at these positions with the risk of PE.

Methods

PubMed, Scopus, Science Direct, Hinari, and African Journal Online databases and Google Scholar search engines were utilized to search studies published in English-language until 30 January 2023. The Joanna Briggs Institute Meta-Analysis instrument was used for data extraction process and the Newcastle-Ottawa Scale was used to appraise the quality of the included studies. Meta-regression analysis was conducted using Stata 14 statistical software. The pooled odds ratios (ORs) of fixed and random effect models were utilized to evaluate the association of eNOS gene polymorphism with the risk of PE at 95% CI. Publication bias was assessed using Egger’s test and a funnel plot.

Results

The study included 47 observational studies involving 13,795 pregnant women (6216 cases and 7579 controls). Pregnant women carrying TT and CC genotypes of eNOS gene at 894 and 786 positions were found to have a greater probability of developing PE as compared to GG and TT genotypes (OR = 1.54 vs. 1.43 and CI: 1.12 − 2.14 vs.1.02 – 2.00 at 95% CI), respectively. However, a significant association was not observed between aa genotype of eNOS gene in VNTR intron-4 region and risk of PE as compared to bb genotype (OR =1.26, 95% CI: 0.83 – 1.89). The allelic model of eNOS gene at all positions showed nonsignificant association with the risk of PE.

Conclusions

The women having eNOS gene variants at 894 and 786 positions showed a significant association with the risk of PE. Yet, the women having eNOS gene variant at intron-4 region showed nonsignificant association with the risk of PE. Thus, this study suggests that eNOS gene variants may play a role in the development of PE, but large-scale studies are required to inaugurate concrete evidence on the roles of eNOS gene variants in PE pathogenesis.

Keywords:

• Nitric oxide synthase type III
• polymorphism
• gene
• pre-eclampsia

Acknowledgment

Not applicable.

Authors’ contributions

ET: Conceptualization, data curation, formal analysis, methodology, writing original draft, writing review, and editing. AM: Conceived the review topic, reviewed the protocol, supervised the review process, reviewed, and validated the final manuscript. EN and STG: Involved in analysis, software work, and reviewing and validating the final manuscript. All authors read and approved the final draft of the manuscript.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Availability of data and materials

All data pertaining to this study are contained and presented in this document and in the supplementary files.

Additional information

Funding

No fund was received for this study.