The Effect of PPARγ rs1801282 Variant on Mortality Risk Among Asians With Chronic Kidney Disease: A Cohort Study and Meta-Analysis

Wei-Teing Chen; Chih-Chien Chiu; Dung-Jang Tsai; Pi-Shao Ko; Meng-Chang Lee; Hsiao-Ting Lin; Ying-Kai Chen; Wen Su; Yuh-Feng Lin; Sui-Lung Su

doi:10.3389/fgene.2022.705272

The Effect of PPARγ rs1801282 Variant on Mortality Risk Among Asians With Chronic Kidney Disease: A Cohort Study and Meta-Analysis

Front Genet. 2022 Feb 21:13:705272. doi: 10.3389/fgene.2022.705272. eCollection 2022.

Authors

Wei-Teing Chen^{1

2}, Chih-Chien Chiu³, Dung-Jang Tsai^{4

5}, Pi-Shao Ko^{4

5}, Meng-Chang Lee⁴, Hsiao-Ting Lin⁴, Ying-Kai Chen^{4

6}, Wen Su⁷, Yuh-Feng Lin^{8

9}, Sui-Lung Su⁴

Affiliations

¹ Division of Chest Medicine, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan.
² National Defense Medical Center, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan.
³ Division of Infectious Diseases, National Defense Medical Center, Department of Internal Medicine, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan.
⁴ School of Public Health, National Defense Medical Center, Taipei, Taiwan.
⁵ National Defense Medical Center, Graduate Institute of Life Sciences, Taipei, Taiwan.
⁶ Division of Nephrology, Department of Medicine, Zuoying Branch of Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan.
⁷ National Defense Medical Center, Graduate Institute of Aerospace and Undersea Medicine, Taipei, Taiwan.
⁸ Division on Nephrology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
⁹ Division of Nephrology, National Defense Medical Center, Department of Medicine, Tri-Service General Hospital, Taipei, Taiwan.

Abstract

Background: Chronic kidney disease (CKD) is a public health issue, and an independent risk factor for cardiovascular disease. The peroxisome proliferator-activated receptor gamma (PPARG) plays an important role in the cardiovascular system. Previous studies have examined one important exon polymorphism, Pro12Ala, in PPARG with respect to mortality of CKD patients, but the results were inconsistent and current evidence is insufficient to support a strong conclusion. This study aimed to examine the correlation between Pro12Ala gene polymorphism and mortality among Asians with CKD by trial sequential analysis (TSA). Methods: The research was divided into observational research and meta-analysis. For the cohort study, 767 subjects from dialysis centers in Taipei were selected as samples, and tracked from December 2015 to February 2017. For the meta-analysis, relevant literature from "PubMed" and "Embase" databases (until December 2016), was searched and TSA was used to verify the results. In order to achieve the best evidence hierarchies, our retrospective cohort study was added to the meta-analysis and the TSA. Results: The combined sample size for Asian was 1,685 after adding our cohort study, and there was no significant correlation between PPARG Pro12Ala and mortality by the allele model (RR: 0.85, 95% CI: 0.39-1.83, I² = 79.3%). Under the parameter setting with the RR value of 1.5, TSA estimation presented that the cumulative sample size entered into the futility area, and it confirmed the conclusion in this study. Conclusion: We found that PPARG Pro12Ala gene polymorphism was not related to mortality in CKD Asians patients, and validated our conclusion using TSA after adding our sample.

Keywords: chronic kidney disease; gene polymorphism; meta-analysis; mortality; peroxisome proliferator-activated receptor gamma; trial sequential analysis.