Table2_The Effect of PPARγ rs1801282 Variant on Mortality Risk Among Asians With Chronic Kidney Disease: A Cohort Study and Meta-Analysis.DOCX

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.

背景：慢性肾脏病（Chronic kidney disease, CKD）是一项公共卫生问题，同时也是心血管疾病的独立危险因素。过氧化物酶体增殖物激活受体γ（peroxisome proliferator-activated receptor gamma, PPARG）在心血管系统中发挥重要作用。既往已有研究针对PPARG基因的重要外显子多态性位点Pro12Ala与慢性肾脏病患者死亡率的相关性展开探讨，但研究结果并不一致，当前证据尚不足以支持明确的结论。本研究旨在通过试验序贯分析（trial sequential analysis, TSA）探讨亚洲慢性肾脏病患者中Pro12Ala基因多态性与死亡率的关联。
方法：本研究分为观察性研究与荟萃分析两部分。在队列研究层面，我们招募了台北透析中心的767名受试者作为研究样本，于2015年12月至2017年2月期间开展随访。在荟萃分析层面，我们检索了"PubMed"及"Embase"数据库截至2016年12月的相关文献，并采用试验序贯分析对研究结果进行验证。为获得最优证据等级，本回顾性队列研究数据被纳入本次荟萃分析与试验序贯分析。
结果：纳入本回顾性队列研究数据后，亚洲人群的合并样本量达1685例。等位基因模型分析显示，PPARG Pro12Ala多态性与死亡率无显著相关性（相对风险RR: 0.85，95%置信区间CI: 0.39–1.83，I²=79.3%）。在RR值设定为1.5的参数条件下，试验序贯分析结果显示累积样本量已进入无效域，证实了本研究的结论。
结论：本研究发现，PPARG Pro12Ala基因多态性与亚洲慢性肾脏病患者的死亡率无显著关联，并在纳入本研究样本后通过试验序贯分析验证了上述结论。