Functional annotation of HBV-associated host genetic variants in the Saudi population: A bioinformatic analysis for precision hepatitis B research

Chronic hepatitis B virus (HBV) infection poses a global public health challenge, for which an effective cure remains elusive. A substantial amount of data has shown that single nucleotide polymorphisms (SNPs) within host genes can affect the regulation and expression of proteins, thereby influencing the susceptibility to HBV infection as well as disease progression and response to treatment. HBV-related SNPs have been identified in the population of the Kingdom of Saudi Arabia (KSA), however, there is a lack of in-depth characterization of the translational and functional impact of these SNPs. This narrative review summarizes and functionally contextualizes the twenty-three reported SNPs across ten genes that showed significant association with HBV-related complications within the Saudi population. These genetic variants are primarily involved in immune signaling, interferon response, and inflammatory regulation pathways, indicating their potential influence on host-virus interactions and disease progression. Using bioinformatic prediction tools, their possible functional impacts were evaluated, providing insights into their biological relevance. The review also highlights future research directions for HBV genomics in Saudi Arabia. Collectively, these findings could contribute to the development of more effective preventive and therapeutic strategies through personalized management of HBV infection. • SNPs in HLA, NOD2, MD2, IL28B, and IL37 alter immunity and may influence HBV risk in the Saudi population. • MD2, IL28B, and IL37 variants linked to HBV clearance; potential immune biomarkers. • Validation and functional studies are needed to enable precision HBV care. • Host SNP profiling may guide precision prevention and risk stratification.