Association of miRNA146a G>C and miRNA196a-2 C>T Gene Polymorphisms with Outcome of Kidney Transplantation in Iranian Patients

Abstract

Acute organ rejection remains a serious clinical challenge. Novel accessible biomarkers of acute rejection could easily enable us to detect the rejection earlier and make more fine-tuned calibration of immunosuppressive or new target treatment possible. Control of gene expression by microRNAs influences many cellular functions, including cellular differentiation, cell proliferation, cell development, and functional regulation of the immune system. Therefore, this study was aimed to investigate if miRNA146a G>C and miRNA196a-2 C>T gene polymorphisms are associated with kidney transplant rejection in Iranian patients. Tissue samples were collected from 100 renal transplant patients between the years 2009 and 2013. The miRNA146a G>C (rs2910164) and miRNA196a-2 C>T (rs11614913) gene polymorphisms were evaluated in kidney transplant patients; using the in-house-polymerase chain Reaction-restriction fragment length polymorphism (PCR-RFLP) method. In this study, we found that the CC genotype, C and G alleles of the miRNA146a G>C polymorphism was associated with increased risk of transplant rejection in kidney transplant patients (p=0.003, p=0.01 and p=0.01), respectively. The CC genotype, T, and C alleles of the miRNA196a-2 C>T were also significantly more frequent in transplanted patients compared to healthy controls (p=0.02, p=0.05, and p=0.05), respectively. However, significant associations were not found between miRNA196a-2 C>T polymorphisms and kidney transplant rejection. The CC genotype, G, and C allele of the miRNA146a G>C and also, the CC genotype, T and C alleles of the miRNA196a-2 C>T may be genetically susceptible factors for transplant rejection and development of kidney disorders, especially in Iranian patients. Further studies are required to validate these findings in a larger population, as well as in patients with different ethnic origins.