Hepatitis B virus may cause either acute or chronic liver infection. It may also involve in liver cirrhosis and hepatic-cellular carcinoma. Chronic infection with HBV is a major worldwide health problem despite the availability of vaccine (Wiegand et al.,2010). The HBV infection prevalence is highly changeable as estimated more than 10% in some Western Pacific countries and Asian’s to under 0.5% in the northern European countries and United States. Viral infections are increasing day by day (Saeed U et al., 2021). Globally the estimated HBV infected individuals are 350 million (Piracha et al., 2018; Saeed et al., 2019; Piracha et al., 2020). Approximately 7–9 million carriers of HBV are found in Pakistan with an increase in carrier rate of 3–5 (Ali et al., 2009). The lifecycle of HBV has been studies exclusively however, the host factors involved in HBV replication and HBV associated HCC mechanisms are not fully understood.
The high mobility group (HMG) proteins binds to nucleosomes in non-sequence specific manner and have the ability to bring structural changes in chromatin (Reeves, 2010). HMG proteins belonged to three families: HMGA, HMGB, and HMGN. These members are structurally divergent but share functional similarity (Reeves, 2010). The most abundant protein of this family is HMGB (high-mobility group box) which is further divided into four groups (HMGB1, HMGB2, HMGB3 and HMGB4) (Reeves, 2010). HMG-box family showcases diversity of characters including chromatin remodeling, transcription, replication, repair, recombination and genomic stability, moreover extracellular HMGB1 involves in cell growth and mitotic activity, receptor signaling(Reeves, 2010). This emphasis that HMGB1 plays a critical role in the pathogenesis and treatment of liver diseases.
A single nucleotide polymorphism (SNP) is the stable replacement of single base in human gene. It is considered the most common genetic mutation in humans appearing in more than 1% of population. SNP is not identified as a disease causing variant, but genetic variation may impact suggestively on the disease susceptibility (Day, 2005; Karlsen et al., 2010). Common and rare SNPs and structural genomic changes may influence or restrict HCC development. Early identification of moderate to high genetic variants associated with HBV-related HCC will help to determine susceptibility of infection better outcomes (Thomas et al., 2009; Brennan et al., 2011; Michailidou et al., 2015). For instance, mutational screening for BRCA1 and BRCA2 is used to identify women at risk for breast and ovarian cancer and is routinely used in accuracy of treatment protocols (Brennan et al., 2011; Michailidou et al., 2015). It is already a known fact that HBV infection is closely related with cytokines and polymorphisms of cytokine gene (ESR1) is reported to be associated with HBV infection (Yan et al., 2012; Deng et al., 2005). One of the SNP rs3742305 was identified in HMGB1 in HBV infected Chinese patients (Deng et al, 2013). Since there is no evidence of reported SNP in Pakistani population, identifying the association of HMGB1 and HBV. We first time reported the study based on polymorphism of HMGB1 gene in HBV patients identified in population of Pakistan origin.