Association of MicroRNA 196a and 499 Polymorphisms with Development of Cirrhosis and Hepatocellular Carcinoma Post-HCV Infection in Egyptian Patients.

Asmaa Mohamed Fteah,Asmaa Ismail Ahmed,Nehad Ahmed Mosaad,Mona Mohamed Hassan,Sherif Hamdy Mahmoud

doi:10.31557/apjcp.2019.20.11.3479

Abstract

Hepatocellular carcinoma (HCC) is the commonest primary tumor of the liver. Chronic HCV infection is the leading cause of end-stage liver disease, HCC and liver-related death in Egypt. Single nucleotide polymorphisms (SNPs) in microRNAs were reported to increase susceptibility to tumorigenesis; affect prognosis and as promising biomarkers in virus-host interactions. This study was conducted to investigate the role of genetic variants of miR-196a2 (rs 11614913) C>T and miR-499 (rs 3746444) A>G in the development of cirrhosis and HCC in Egyptian HCV infected patients. Genotyping of the candidate SNPs was performed by Real Time PCR in 75 HCV-related HCC patients, 75 cirrhotic patients on top of HCV and 75 healthy controls. There was significant difference in miR-499 (rs3746444) genotypes frequency between the three studied groups as the GG genotype was significantly lower in HCC cases than other groups (P = 0.009) while the combined miR-499 (AA+AG) genotypes were significantly higher in HCC cases than other groups (P = 0.005). Also a significant difference was found in miR-499 genotypes frequency when compared between HCC and cirrhosis groups as the GG genotype was significantly lower in HCC cases than cirrhosis group (P = 0.006) while the combined miR-499 (AA+AG) genotypes were significantly higher in HCC cases than in cirrhosis group (P = 0.003) [OR (95% CI) = 0.131 (0.028-0.601)]. The frequency of the G allele was significantly lower in HCC than other groups (P = 0.024) and significantly lower in HCC than normal group (P = 0.006) [OR (95%CI) = 0.501 (0.304-0.825)]. For miR-196a2 (rs11614913) C>T polymorphisms, no significant association was found with HCC risk. Our study concluded that the G allele of miR-499 is associated with lower risk of HCV related HCC development. No significant association of miR-196a2 (rs 11614913), genotypes or alleles with risk for HCC development, could be detected.

Highlights

Hepatocellular carcinoma is the fifth most common tumor worldwide and the second most common cause of cancer-related death (Choo et al, 2016)
There was significant difference in miR-499 genotypes frequency between the three studied groups as the GG genotype was significantly lower in Hepatocellular carcinoma (HCC) cases than other groups (P = 0.009) while the combined miR-499 (AA+AG) genotypes were significantly higher in HCC cases than other groups (P = 0.005)
A significant difference was found in miR-499 genotypes frequency when compared between HCC and cirrhosis groups as the GG genotype was significantly lower in HCC cases than cirrhosis group (P = 0.006) while the combined miR-499 (AA+AG) genotypes were significantly higher in HCC cases than in cirrhosis group (P = 0.003) [odd’s ratio (OR) = 0.131 (0.028-0.601)]

Summary

Introduction

Hepatocellular carcinoma is the fifth most common tumor worldwide and the second most common cause of cancer-related death (Choo et al, 2016). According to Globocan (2012), HCC is the first most common cancer in men and the second most common cancer in women in Egypt. Chronic HCV infection is considered an independent risk factor for liver cirrhosis and HCC (Mohd Hanafiah et al, 2013). According to Egyptian Demographic Health Survey (EDHS) 2015; the seroprevalence of HCV was 10% in the age groups 15–59 years in Egypt (Gomaa et al, 2017). HCC management requires a multidisciplinary approach because of the wide heterogenecity in clinical manifestations, differences in biologic behaviour, different causes of chronic liver disease and different therapeutic protocols (Abdelaziz et al, 2014)

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