Objective: To investigate the relationship between mutations of rtM204V/I (methionine to valine or isoleucine at position rt204 of reverse transcriptase domain) in the hepatitis B virus (HBV) polymerase gene and the G1896A and G1899A single mutations in the pre-eore (PC) region and the A1762T and G1764A double-mutations in the basal core promoter (BCP) region.
Methods: A total of 2,849 hepatitis B complete genome sequences were retrieved from the GenBank/EMBL/DDBJ. The amino acid sequence of the of reverse transcriptase domain and genome sequences of the PC region and the BCP region were aligned using MEGA4 software. Data were calculated using Microsoft Excel and evaluated using SPSS 13.0 statistical software.
Results: Among the 2, 849 HBV complete genome sequences, 217 (8%) strains were identified with Y(I/V) DD and 120 of those had the YIDD mutation and 97 had the YVDD mutation. Of the 1543 strains (54.2%) with PC-BCP mutations, seven mutation patterns of G 1896A-G 1899A-G 1896A-G 1899A-A 1762T/G 1764A, A 1762T/G 1764AG 1896A, A 1762T/G 1764A-G 1899A, and A 1762T/G 1764A-G 1896A-G 1899A were identified. of YMDD and PC-BCP had a higher incidence than the single YMDD mutation (76% vs 24.0%, x2=45.283, P=0.000). The double-mutations of YIDD and PC-BCP had a higher incidence than the double-mutation of YVDD and PC-BCP (85% vs 64.9%, x2=11.836, P=0.000). The double-mutation for lamivudine resistance of YMDD and PC-BCP had a higher incidence than the double pre-existent YMDD and PC-BCP mutations (89.3% vs 58.9%, x2=27.084, P=0.000). The three mutation patterns of G1896A-G1899A (P=0.000, OR=7.573), A1762T/G1764A-G1899A (P=0.000, OR=6.539) and A1762T/G1764A-G1896A-G1899A (P=0.000, OR=6.596) were associated with a greater risk of developing the YIDD mutation, according to binary logistic analysis.
Conclusion: There is a relationship between the HBV YI/VDD mutation and PC-BCP mutations. Different PC-BCP mutation patterns have different effects on the YI/VDD mutation.