Evaluation of microRNA Gene Polymorphisms in Liver Transplant Patients with Hepatocellular Carcinoma

Abstract

Background: Genetic polymorphism in the miRNA sequence might alter miRNA expression and/or maturation, which is associated with the development and progression of hepatocellular carcinoma (HCC) in liver transplant patients. Objectives: Therefore, the prevalence of miRNA-146a G > C (rs2910164), miRNA-499A > G (rs3746444), miRNA-149C > T (rs2292832), and miRNA-196a-2 C > T (rs11614913) gene polymorphisms was evaluated in liver recipients with HCC with or without experiencing graft rejection. Methods: In a cross-sectional study, tissue samples were collected from 60 HCC patients who underwent liver transplant surgery at Namazi Hospital, Shiraz, Iran, in 2013 - 2015. A control group consisting of 120 individuals was randomly selected, as well. The genomic DNA was extracted from collected tissues and blood samples. The miRNA-146a (rs2910164), miRNA-499 (rs3746444), miRNA-149 (rs2292832), and miRNA-196a-2 (rs11614913) gene polymorphisms were evaluated in patients with HCC using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Results: The CC genotype and C allele of the miRNA-146a (rs2910164) polymorphism were significantly associated with the increased risk of transplant rejection in patients with HCC (P = 0.05 and P = 0.05, respectively). The CC genotype and C allele of the miRNA-146a (rs2910164) were also significantly more frequent in male liver transplant patients who experienced acute rejection than in non-rejected ones (P = 0.05 and P = 0.03, respectively). However, no significant association was found between the genotypes and alleles of miRNA-499 (rs3746444), miRNA-149 (rs2292832), and miRNA-196a-2 (rs11614913) polymorphisms and HCC outcomes in liver transplant recipients. Conclusions: The importance of the CC genotype and C allele of the miRNA-146a (rs2910164) polymorphism in increasing the risk of transplant rejection was confirmed, but it needs further studies in larger populations.