Genetic variants of MicroRNA-related genes in susceptibility and prognosis of end-stage renal disease and renal allograft outcome among north Indians

摘要

BACKGROUND AND AIM: MicroRNAs are important molecules of the innate and adaptive immune system, which may play an important role in maintaining normal immune homeostasis. The aim of this study was to investigate the impact of MIR146A C>G (rs2910164), MIR149 T>C (rs2292832), MIR196A2 T>C (rs11614913), and MIR499A A>G (rs3746444) single nucleotide polymorphisms (SNPs) among end-stage renal disease (ESRD) and acute allograft rejection (AR) cases. MATERIALS AND METHODS: Genotyping of MicroRNA SNPs was performed using a PCR, followed by restriction fragment length polymorphism in 350 ESRD patients and 350 age-matched, sex-matched, and ethnically matched controls. RESULTS: We observed an increased risk of almost two-fold for ESRD and three-fold for AR cases under univariate and multivariate models for mutant genotypes of rs2910164, rs11614913, and rs3746444 SNPs. Subsequently, no susceptible/ protective effect was observed for rs2292832 SNP with ESRD and AR cases. Interestingly, all the SNPs that were significant after multiple comparisons in ESRD and AR cases remained significant in the bootstrap analysis, providing internal validation to our initial observations. Survival analysis showed that the mutant genotypes of rs2910164, rs11614913, and rs3746444 SNPs were associated with the lowest overall survival compared with heterozygous and wild genotypes among renal allograft recipients. The crude and adjusted hazard ratios in univariate and multivariate Cox regression models showed an almost two-fold increased risk for overall survival against mutant genotypes of rs2910164, rs11614913, and rs3746444 SNPs in renal allograft recipients. CONCLUSION: These results suggest that the variants of MicroRNA SNPs, namely, rs2910164, rs11614913, and rs3746444, might be involved in susceptibility to ESRD and AR.