Autophagy Genes ATG16L1 and IRGM Variants and Hepatitis B Virus Infection Susceptibility

Abstract

Hepatitis B virus infection is a severe liver inflammation and is the main cause of morbidity and mortality in developing countries. Along with the environmental factors and virus-related factors, host genetic factors also play an imperative role in HBV pathogenesis and disease outcome. Host genetic factors are known as an important factor in patient s susceptibility to HBV infection. Recently, a large number of studies reported the connection of many viral infections with the autophagy process. Moreover, HBV also enhances the autophagy process, without promoting protein degradation and use the process for its own replication. Single Nucleotide Polymorphisms (SNPs) in the autophagy genes are strongly associated with many diseases such as Crohn s disease, asthma, cancer, Paget disease of bones, and various neurodegenerative diseases. Understanding of molecular mechanism of autophagy pathway and its modulation could be helpful in the management of liver diseases including HBV infection. IRGM and ATG16L1 are two important genes of autophagy pathway, which helps in the initiation and autophagosome formation. Various association studies documented the role of SNPs in these genes with many diseases. However, no association studies have been conducted to see the role of SNPs of IRGM and ATG16L1 genes with HBV infection. In this study, we have genotyped three promoter region SNPs (rs4958842, rs4958843 and rs4958846) of IRGM gene and three intronic (rs2241879, rs13005285, and rs7587633) and one exonic (rs2241880) SNP of ATG16L1 gene in 551 HBV infected and 247 healthy control individuals. HBV infected individuals belong to different clinical categories such as asymptomatic, acute, chronic hepatitis B and liver cirrhosis. HBV DNA levels and plasma AST and ALT levels were also correlated with different genotypes of the SNPs. In case of IRGM SNPs, we found the protective association of the SNP rs4958842 and rs4958846 with HBV infection and rs4958843 was associated with HBV infection susceptibility.