Ying Daojing, Jiang Mengjie, Rong Liping, Zhuang Hongjie, Chen Lizhi, Xu Yuanyuan, Jiang Xiaoyun
Department of Pediatric Nephrology and Rheumatology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Front Pediatr. 2021 Oct 15;9:724258. doi: 10.3389/fped.2021.724258. eCollection 2021.
Studies have identified that MIF -173 G>C gene polymorphism is associated with idiopathic nephrotic syndrome (INS) susceptibility and steroid resistance, but the results remain inconclusive. We searched PubMed, Embase, and Web of Science for relevant studies published before 31 March 2021. Pooled data were reported as odds ratio (OR) with 95% confidence interval (CI). Noteworthiness of significant OR was estimated by the false positive report probability (FPRP) test. Trial sequential analysis (TSA) was used to control type I and type II errors. We selected seven case-control studies that included 1,026 INS children (362 were steroid-resistant NS and 564 were steroid-sensitive NS) and 870 controls. The results showed that MIF -173 G>C polymorphism was significantly associated with INS susceptibility in allelic, heterozygous and dominant genetic models (C vs. G: OR = 1.325, 95% CI: 1.011-1.738; GC vs. GG: OR = 1.540, 95% CI: 1.249-1.899; CC + GC vs. GG: OR = 1.507, 95% CI: 1.231-1.845), and FPRP test and TSA indicated that the associations were true in heterozygous and dominant models. The pooled results also revealed that MIF -173 G>C polymorphism was significantly associated with steroid resistance in allelic, homozygous and recessive models (C vs. G: OR = 1.707, 95% CI: 1.013-2.876; CC vs. GG: OR = 4.789, 95% CI: 2.109-10.877; CC vs. GC + GG: OR = 4.188, 95% CI: 1.831-9.578), but FPRP test indicated that all these associations were not noteworthy. Furthermore, TSA revealed that the non-significant associations between MIF -173 G>C polymorphism and steroid resistance in heterozygous and dominant models were potential false negative. This meta-analysis could draw a firm conclusion that MIF -173 G>C polymorphism was significantly associated with increased INS risk in heterozygous and dominant genetic models. MIF -173 G>C polymorphism was not likely to affect steroid responsiveness, but more studies were needed to confirm.
研究已确定MIF -173 G>C基因多态性与特发性肾病综合征(INS)易感性及类固醇抵抗相关,但结果仍无定论。我们检索了PubMed、Embase和Web of Science,以查找2021年3月31日前发表的相关研究。汇总数据以比值比(OR)及95%置信区间(CI)报告。通过假阳性报告概率(FPRP)检验评估显著OR的显著性。采用序贯试验分析(TSA)控制I型和II型错误。我们选择了7项病例对照研究,其中包括1026名INS儿童(362名对类固醇耐药的NS患者和564名对类固醇敏感的NS患者)及870名对照。结果显示,在等位基因、杂合子和显性遗传模型中,MIF -173 G>C多态性与INS易感性显著相关(C vs. G:OR = 1.325,95% CI:1.011 - 1.738;GC vs. GG:OR = 1.540,95% CI:1.249 - 1.899;CC + GC vs. GG:OR = 1.507,95% CI:1.231 - 1.845),FPRP检验和TSA表明在杂合子和显性模型中这些关联是真实的。汇总结果还显示,在等位基因、纯合子和隐性模型中,MIF -173 G>C多态性与类固醇抵抗显著相关(C vs. G:OR = 1.707,95% CI:1.013 - 2.876;CC vs. GG:OR = 4.789,95% CI:2.109 - 10.877;CC vs. GC + GG:OR = 4.188,95% CI:1.831 - 9.578),但FPRP检验表明所有这些关联均无显著性。此外,TSA显示在杂合子和显性模型中MIF -173 G>C多态性与类固醇抵抗之间的非显著关联可能为假阴性。这项荟萃分析可以得出一个明确的结论,即MIF -173 G>C多态性在杂合子和显性遗传模型中与INS风险增加显著相关。MIF -173 G>C多态性不太可能影响类固醇反应性,但需要更多研究来证实。