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

• Published in: PloS one Vol. 16; no. 10; p. e0258789
• Main Authors: Hsiao, Po-Jen, Chiu, Chih-Chien, Tsai, Dung-Jang, Ko, Pi-Shao, Chen, Ying-Kai, Cheng, Hao, Su, Wen, Lu, Kuo-Cheng, Su, Sui-Lung
• Format: Journal Article
• Language: English
• Published: San Francisco Public Library of Science 18.10.2021; Public Library of Science (PLoS)
• Subjects: Analysis; Armed forces; Biology and Life Sciences; Chronic kidney failure; Confidence intervals; Diabetes; Dialysis; Functional analysis; Gene expression; Gene polymorphism; Genetic aspects; Genetic polymorphisms; Glomerular filtration rate; Hemodialysis; Hospitals; Hypertension; Internal medicine; Kidney diseases; Kidneys; Life sciences; Medicine; Medicine and Health Sciences; Meta-analysis; Nephrology; Nitric oxide; Nitric-oxide synthase; Physical Sciences; Polymorphism; Public health; Research and Analysis Methods; Sample size; Sequential analysis; Taiwan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0258789

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. 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. 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) [greater than or equal to] 60 mL/min/1.73 m.sup.2, 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. 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. 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.