OBJECTIVETo investigate the relationship between the mutation patterns of rtM204V/I (methionine to valine or isoleucine at position rt204 of reverse transcriptase domain) in hepatitis B virus (HBV) polymerase gene and HBV genotypes.

METHODSA total of 2849 HBV complete genome sequences were retrieved from the GenBank/EMBL/DDBJ. HBV genotypes were determined by using MEGA4 software. The amino acid sequences of the reverse transcriptase (RT) domain were aligned. Data were analyzed using SPSS 13.0. RESULTS Among the 2849 HBV complete genome sequences, 217 strains with Y (I/V) DD were identified. Of them, 120 had YIDD mutation and the genotype/subgenotype distribution was as follows: A (2), B(B2 19), C(C1 1, C2 78, C5 1), D(17), E(1), G(1); 97 had YVDD mutation and the genotype/subgenotype distribution was as follows: A(17), B(B2 22), C(C1 3, C2 48), D(3), G(3), H(1). There is a significant difference in the mutation patterns of Y (I/V) DD among genotypes of A-D, A-C, and between genotype A and B, P < 0.01.There is a difference in the mutation pattern of Y (I/V) DD among genotypes of B-D, between genotype C and D, P < 0.05. Genotype A has a higher tendency to develop YVDD mutation, whereas genotype D has a higher frequency to develop YIDD mutation. The rtM204V-rtL180M mutations were more frequently found in subgenotype B2 than in subgenotype C2 while the rtM204V-rtL180M-rtV173L mutations were more associated with subgenotype C2 (P < 0.01).

CONCLUSIONDifferent HBV genotype/subgenotype may select different mutation pattern in the YMDD domain. Subgenotype C2 is more diversity and complexity than other HBV genotypes/subgenotypes.