Ann Lab Med 2019; 39(1): 58-66  https://doi.org/10.3343/alm.2019.39.1.58
Association of MicroRNA Polymorphisms With Hepatocellular Carcinoma in an Iranian Population
Zhaleh Farokhizadeh, M.Sc1, Sahar Dehbidi, M.Sc1, Bita Geramizadeh, M.D.2, Ramin Yaghobi, Ph.D.2, Seyed Ali Malekhosseini, M.D.2, Mehrdad Behmanesh, Ph.D.3, Mohammad Hossein Sanati, Ph.D.1, Afsoon Afshari, Ph.D.2, Ali Moravej, Ph.D.4, and Mohammad Hossein Karimi, Ph.D.2
1Nour Danesh Institute of Higher Education, Mimeh, Iran; 2Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; 3Genetic Department, Tarbiat Modarres University, Tehran, Iran; 4Noncommunicable Diseases Research Centre, Fasa University of Medical Sciences, Fasa, Iran
Corresponding author: Mohammad Hossein Karimi, Ph.D.
https://orcid.org/0000-0002-2435-6277
Transplant Research Center, Shiraz University of Medical Sciences, Shiraz 71345-1978, Iran
Tel: +9891 7314 9022
Fax: +9871 3647 3954
E-mail: karimimh@sums.ac.ir
Received: September 10, 2017; Revised: December 6, 2017; Accepted: August 16, 2018; Published online: January 1, 2019.
© Korean Society for Laboratory Medicine. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Single nucleotide polymorphisms (SNPs) can modulate various biological processes by influencing microRNA (miRNA) biogenesis and altering target selection. Common SNPs may alter the processing of miRNA and may be associated with hepatocellular carcinoma (HCC). We investigated the relationship between miR-499A>G, miR-149C>T, miR-196a2T>C, and miR-146aG>C and HCC susceptibility, examining the interaction of the miRNAs with hepatitis B virus (HBV).
Methods: We evaluated the associations of miR-499A>G (rs3746444), miR-149C>T (rs2292832), miR-196a2T>C (rs11614913), and miR-146aG>C (rs2910164) with HCC susceptibility in 100 HCC patients (70 males and 30 females) and 120 healthy controls (70 males and 50 females), using the PCR-restriction fragment length polymorphism method.
Results: For miR-499A>G, the frequencies of the AG genotype and G allele were higher in female HCC patients than in female controls (P=0.02 and 0.045, respectively). The frequency of the A allele was higher in HBV-positive HCC patients than in controls (P=0.019). For miR-149C>T, the frequency of the CC genotype was higher in female HCC patients than in female controls (P=0.009). For miR-196a2T>C, the frequencies of the CT and CC genotypes and the C allele were higher in HBV-positive HCC patients than in controls (P<0.001, P=0.009, and P<0.001, respectively). The frequencies of miR-146aG>C polymorphisms did not differ between HCC patients and controls.
Conclusions: miR-499A>G, miR-149C>T, and miR-196a2T>C were associated with the development of HCC in women and/or that of HBV-related HCC. They can be considered genetic risk factors for the development of HCC among Iranians.
Keywords: Single nucleotide polymorphism, MicroRNA, Hepatocellular carcinoma, Hepatitis B virus



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