Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis.
<h4>Background</h4>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 size...
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oai:doaj.org-article:c65e3cddf439473d82e9903bfa5de78e2021-12-02T20:16:49ZAssociation between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis.1932-620310.1371/journal.pone.0258789https://doaj.org/article/c65e3cddf439473d82e9903bfa5de78e2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0258789https://doaj.org/toc/1932-6203<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.Po-Jen HsiaoChih-Chien ChiuDung-Jang TsaiPi-Shao KoYing-Kai ChenHao ChengWen SuKuo-Cheng LuSui-Lung SuPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0258789 (2021) |
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Medicine R Science Q 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 Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis. |
| description |
<h4>Background</h4>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.<h4>Objective</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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. |
| format |
article |
| author |
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 |
| author_facet |
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 |
| author_sort |
Po-Jen Hsiao |
| title |
Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis. |
| title_short |
Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis. |
| title_full |
Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis. |
| title_fullStr |
Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis. |
| title_full_unstemmed |
Association between nitric oxide synthase T-786C genetic polymorphism and chronic kidney disease: Meta-analysis incorporating trial sequential analysis. |
| title_sort |
association between nitric oxide synthase t-786c genetic polymorphism and chronic kidney disease: meta-analysis incorporating trial sequential analysis. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2021 |
| url |
https://doaj.org/article/c65e3cddf439473d82e9903bfa5de78e |
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