Intronic region polymorphisms, rs2241879 G/A, rs13005285 G/T, and rs7587633 C/T of ATG16L1 were analyzed in this case-control study in HBV-infected patients to find their role in HBV infection. The mutant alleles rs2241879A (OR = 1.57) and rs13005285T (OR = 1.39) were the risk factors for HBV infection. These alleles were associated with different stages of infection: asymptomatic rs13005285T (OR = 1.91), acute rs13005285T (OR = 1.58), chronic rs2241879A (OR = 1.62), and cirrhosis rs2241879A (OR = 3.02). Moreover, on applying various genetic models, rs2241879A predisposed individuals to HBV infection (homozygous model
AA vs. GG
OR = 2.58). Patients with CHB infection, the homozygous model showed an OR of 2.79, while the dominant model had an OR of 1.96. Among cirrhosis patients, the homozygous model resulted in an OR of 9.43, and the dominant model showed an OR of 4.92. The rs13005285 variant significantly increased the risk of acute HBV infection in the co-dominant model (OR = 1.78) and dominant model (OR = 1.84). Individuals with the rs7587633 variant at the asymptomatic stage of infection showed a reduced risk under the co-dominant model (OR = 0.41) and the dominant model (OR = 0.54). We identified GCG, GTG and GCT haplotypes corresponding to rs2241879, rs7587633, and rs13005285 SNPs, which play a protective role in HBV infection. Furthermore, we also developed a PCR-ARFLP assay for genotyping rs13005285G/T which would help to analyze this polymorphism in low-income settings where high-end instrumentation is not accessible.