{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:12:39Z","timestamp":1775581959694,"version":"3.50.1"},"reference-count":59,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T00:00:00Z","timestamp":1634515200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007225","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST107-2314-B016-052-MY3, MOST110-2314-B016-006"],"award-info":[{"award-number":["MOST107-2314-B016-052-MY3, MOST110-2314-B016-006"]}],"id":[{"id":"10.13039\/100007225","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Defense Medical Center","award":["MND-MAB-110-105"],"award-info":[{"award-number":["MND-MAB-110-105"]}]},{"name":"Taoyuan Armed Forces General Hospital","award":["TYAFGH-D-110032"],"award-info":[{"award-number":["TYAFGH-D-110032"]}]},{"name":"Taoyuan Armed Forces General Hospital","award":["TYAFGH-D-110023"],"award-info":[{"award-number":["TYAFGH-D-110023"]}]},{"name":"Zuoying Branch Of Kaohsiung Armed Forces General Hospital","award":["KAFGH-ZY-E-110037"],"award-info":[{"award-number":["KAFGH-ZY-E-110037"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Background<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Objective<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Methods<\/jats:title>\n<jats:p>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) \u2265 60 mL\/min\/1.73 m<jats:sup>2<\/jats:sup>, 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Results<\/jats:title>\n<jats:p>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\u20131.46), into a meta-analysis, which supported that eNOS T-786C was significantly associated with CKD in Asians (OR = 1.39, 95% CI = 1.04\u20131.85) 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.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec005\">\n<jats:title>Conclusions<\/jats:title>\n<jats:p>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.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0258789","type":"journal-article","created":{"date-parts":[[2021,10,18]],"date-time":"2021-10-18T18:52:59Z","timestamp":1634583179000},"page":"e0258789","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis"],"prefix":"10.1371","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4965-0285","authenticated-orcid":true,"given":"Po-Jen","family":"Hsiao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chih-Chien","family":"Chiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dung-Jang","family":"Tsai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pi-Shao","family":"Ko","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying-Kai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuo-Cheng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3122-1116","authenticated-orcid":true,"given":"Sui-Lung","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2021,10,18]]},"reference":[{"issue":"7","key":"pone.0258789.ref001","doi-asserted-by":"crossref","first-page":"e0158765","DOI":"10.1371\/journal.pone.0158765","article-title":"Global Prevalence of Chronic Kidney Disease\u2014A Systematic Review and Meta-Analysis","volume":"11","author":"N.R. 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