Association Between Macrophage Migration Inhibitory Factor-173 G>C Gene Polymorphism and Childhood Idiopathic Nephrotic Syndrome: A Meta-Analysis

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

Automated summary

The meta-analysis found that MIF-173 G > C polymorphism was significantly associated with increased susceptibility to idiopathic nephrotic syndrome (INS) in heterozygous and dominant genetic models. However, it was not likely to affect steroid responsiveness. More studies are needed to confirm these findings.