TGF-Β1 & PNPLA3 Genetic Variants and the Risk of Hepatic Fibrosis and HCC in Egyptian Patients with HCV-Related Liver Cirrhosis

Document Type : Research Articles

Authors

1 Department of Chemical Pathology, Medical Research Institute, Alexandria University, Egypt.

2 Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos University, Egypt. Lecturer in the School of Biological Sciences, Faculty of Science, University of East Anglia, UK.

3 Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Egypt.

Abstract

Objective: The clinical outcomes of hepatitis C virus (HCV) infection and its sequelae including liver cirrhosis and hepatocellular carcinoma (HCC) are greatly affected by host genetic factors; however, the possible mechanisms are still largely unclear. This work aimed to assess transforming growth factor-β1 (TGF-β1), and patatin-like phospholipase domain containing-protein 3 (PNPLA3) genetic variants as risk factors for hepatic fibrosis and hepatocellular carcinoma (HCC) in Egyptian patients with HCV-related liver cirrhosis. Methods: Seventy HCV-related liver cirrhosis patients (Total cirrhosis) who were divided into two groups; 34 patients with HCC (HCC group), and 36 patients without HCC (LC group) and 20 healthy volunteers (control group) were included. Routine laboratory investigations and imaging studies were determined. TGF-β1 (Arg25Pro; 915G>C) and PNPLA3 (I148M; C>G) variants were evaluated using real-time polymerase chain reaction (real-time PCR). Results: HCC group showed a significantly higher GG genotype distribution of TGF-β1 (Arg25Pro) than the LC group (P= 0.008, OR: 7.083, CI 95%: 1.422 – 35.282). The distributions of GG genotype (P= 0.047) and G allele (P= 0.002, OR: 4.395, CI 95%: 1.622 – 11.911) of PNPLA3 (I148M) were significantly higher in total cirrhosis patients than controls. Conclusion: TGF-β1 (Arg25Pro) GG variant may be associated with HCC risk in HCV-related liver cirrhosis patients, while PNPLA3 (I148M) GG variant may be associated with cirrhosis development but not HCC risk in HCV-related liver cirrhosis patients. 

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Volume 22, Issue 10
October 2021
Pages 3317-3326
  • Receive Date: 24 June 2021
  • Revise Date: 30 July 2021
  • Accept Date: 13 October 2021
  • First Publish Date: 13 October 2021