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Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis

Author

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  • Po-Jen Hsiao
  • Chih-Chien Chiu
  • Dung-Jang Tsai
  • Pi-Shao Ko
  • Ying-Kai Chen
  • Hao Cheng
  • Wen Su
  • Kuo-Cheng Lu
  • Sui-Lung Su

Abstract

Background: Several meta-analyses of the relationship between endothelial nitric oxide synthase (eNOS) T-786C gene polymorphism and chronic kidney disease (CKD) have been published. However, the results of these studies were inconsistent, and it is undetermined whether sample sizes are sufficient to reach a definite conclusion. Objective: To elucidate the relationship between T-786C and CKD by combining previous studies with our case-control sample and incorporate trial sequential analysis (TSA) to verify whether the sample size is adequate to draw a definite conclusion. Methods: PubMed and Embase databases were searched for relevant articles on eNOS T-786C and CKD before February 28, 2021. TSA was also incorporated to ascertain a conclusion. A total of 558 hemodialysis cases in the case-control study was recruited from nine dialysis centers in the northern area of Taiwan in 2020. Additionally, 640 healthy subjects of the control group, with estimated glomerular filtration rate (eGFR) ≥ 60 mL/min/1.73 m2, were selected from participants of the annual elderly health examination program at the Tri-Service General Hospital. The functional analysis was based on eQTL data from GTExPortal. Results: After screening with eligibility criteria, 15 papers were included and eventually combined in a meta-analysis. The result of the TSA showed that the sample size for Caucasians was adequate to ascertain the correlation between eNOS T-786C and CKD but was insufficient for Asians. Therefore, we added our case-control samples (n = 1198), though not associated with CKD (odds ratio [OR] = 1.01, 95% confidence interval [CI] = 0.69–1.46), into a meta-analysis, which supported that eNOS T-786C was significantly associated with CKD in Asians (OR = 1.39, 95% CI = 1.04–1.85) by using an adequate cumulative sample size (n = 4572) analyzed by TSA. Data of eQTL from GTEx showed that T-786C with the C minor allele exhibited relatively lower eNOS mRNA expression in whole blood, indicating the hazardous role of eNOS T-786C in CKD. Conclusions: eNOS T-786C genetic polymorphism was of conclusive significance in the association with CKD among Asians in our meta-analysis. Our case-control samples play a decisive role in changing conclusions from indefinite to definite.

Suggested Citation

  • Po-Jen Hsiao & Chih-Chien Chiu & Dung-Jang Tsai & Pi-Shao Ko & Ying-Kai Chen & Hao Cheng & Wen Su & Kuo-Cheng Lu & Sui-Lung Su, 2021. "Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis," PLOS ONE, Public Library of Science, vol. 16(10), pages 1-16, October.
    • Handle: RePEc:plo:pone00:0258789
    DOI: 10.1371/journal.pone.0258789
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    1. Nathan R Hill & Samuel T Fatoba & Jason L Oke & Jennifer A Hirst & Christopher A O’Callaghan & Daniel S Lasserson & F D Richard Hobbs, 2016. "Global Prevalence of Chronic Kidney Disease – A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 11(7), pages 1-18, July.
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