Molecular Diversity of Hepatitis B Virus X Gene in Central Kerala, Southern India

Abstract

Introduction: Hepatitis B Virus (HBV) causes diverse clinical manifestations ranging from acute fulminant Hepatitis, Chronic Hepatitis (CHB) to liver cirrhosis and Haepatocellular Carcinoma (HCC). The HBV X gene (HBV-X) is a 154 amino acid multifunctional protein, mutates frequently and has a role in HBV related HCC. Aim: The current study was to explore the genetic variability and identify mutations of HBV-X in CHB patients from Central Kerala, India. Materials and Methods: The HBV-X sequences (n=39) from CHB (n=90) patients were analysed for nucleotide and amino acid diversity. Phylogenetic analyses were done using MEGA version 7.0.21 software to determine different genotypes. Results: Basal Core Promoter (BCP) mutations: A1762T/ G1764A (n=5) were found in HBeAg negative subjects (n=3, 60%). Bioinformatic analysis showed that the substitutions and mutations were HBV genotype/subgenotype specific. The predominant genotype detected was A1 (n=52, 57.77%) followed by genotype D (n=27, 30.00%). Nucleotide and amino acid diversities were more in genotype A1 than in D, which is responsible for transactivation (p<0.0001), those infected with this genotype may be at high risk for HCC. Conclusion: Genotype A1 isolates displayed most mutations/ substitutions in HBV-X, Further studies are necessary to understand its role in contributing to the development of HCC. The study represents the first formal investigation of HBV-X genetic variability in Kerala.

Keywords

• basal core promoter
• chronic hepatitis b
• genotypes
• hepatocellular carcinoma
• x gene mutation