Misra Maneesh K, Pandey Shashi K, Kapoor Rakesh, Sharma Raj K, Agrawal Suraksha
Departments of aMedical Genetics bUrology and Renal Transplantation cNephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow dDepartment of Anatomy, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India.
Pharmacogenet Genomics. 2014 Sep;24(9):442-50. doi: 10.1097/FPC.0000000000000074.
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.
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.
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.
These results suggest that the variants of MicroRNA SNPs, namely, rs2910164, rs11614913, and rs3746444, might be involved in susceptibility to ESRD and AR.
微小RNA是先天性和适应性免疫系统的重要分子，可能在维持正常免疫稳态中发挥重要作用。本研究旨在调查终末期肾病（ESRD）和急性移植排斥反应（AR）病例中MIR146A C>G（rs2910164）、MIR149 T>C（rs2292832）、MIR196A2 T>C（rs11614913）和MIR499A A>G（rs3746444）单核苷酸多态性（SNP）的影响。
采用聚合酶链反应（PCR）对微小RNA SNP进行基因分型，随后对350例ESRD患者和350例年龄匹配、性别匹配及种族匹配的对照进行限制性片段长度多态性分析。
在rs2910164、rs11614913和rs3746444 SNP突变基因型的单变量和多变量模型下，我们观察到ESRD病例风险增加近两倍，AR病例风险增加三倍。随后，未观察到rs2292832 SNP对ESRD和AR病例有易感性/保护作用。有趣的是，在ESRD和AR病例中多次比较后显著的所有SNP在自抽样分析中仍然显著，为我们的初步观察提供了内部验证。生存分析表明，与肾移植受者中的杂合子和野生基因型相比，rs2910164、rs11614913和rs3746444 SNP的突变基因型与总体生存率最低相关。单变量和多变量Cox回归模型中的粗风险比和调整风险比显示，肾移植受者中rs2910164、rs11614913和rs3746444 SNP突变基因型的总体生存风险增加近两倍。
这些结果表明，微小RNA SNP的变体，即rs2910164、rs11614913和rs3746444，可能与ESRD和AR的易感性有关。
