HBx genetic variability was explored in the Eastern Indian population with low HCC incidence. DNase I sensitive HBV DNA was detected in 53% samples, which differed significantly between clinical groups (P<0.001). HBV genotypes A (Aa/A1), C (Cs/C1) and D (D1, D2, D3, D5) were detected in 37.5%, 18.7% and 43.7% samples respectively. Population specific signature HBx residues A(36), V-88, S-101 in Aa/A1 and residues P-41, Q(110) in D5 were detected. Mutations T-27, M-130 and I-131 were detected in 66.7%, 91% and 75% of genotype A, C and D5 samples respectively. Very low occurrence of HCC associated Mutations (V5M/L, P38S, and H94Y) and absence of C-terminal deletions were observed. Our study shows that HBV genotype associated clinically important HBx variations may evolve and act distinctly in different geo-ethnic Populations. Further studies on HBx functions from the perspective of genetic variability are essential for the better understanding of the clinical significance of HBV. (C) 2008 Elsevier Inc. All rights reserved.