To Probe The Relationship Between Hepatitis B Virus Gene Mutations And Lamivudine-Resistant

Objective:To probe the relationship between HBV gene mutations at baseline and HBV DNA rebound and lamivudine-resistant.Methods:54 serum samples of 27 patients with infecting hepatitis B at baseline and HBV DNA rebound after Lamivudine therapy were collected. HBV genotypes were detected by nested PCR with multiple pair primers, mutations at baseline and HBV DAN rebound of polymerase(P), core genes(C),envelope gene(S),X gene(X),basal core promoter(BCP), precore(PC)were analysed by polymerase chain reaction (PCR) direct sequencing approach.Results:(1) In the 27 patients, there were 9 sites mutations of HBV P gene at baseline were detected, and the frequency of rtN/H238T/A,rtL217P/N and rtN248H mutations were higher, respectively 7.4%,7.4% and 7.4%; there were 23 sites mutations of HBV BCP gene at baseline were detected, and the frequency of A1762T,G1764A and A1775G mutations were higher, respectively 40.7%,29.6% and 25.9%; there were 4 sites mutations of HBV PC gene at baseline were detected, and the frequency of T1858C/A and G1896A mutations were higher, respectively 29.6% and 18.5%; there were 25 sites mutations of HBV C gene at baseline were detected, and the frequency of P130T/H,L60V and S87G mutations were higher, respectively 14.8%,14.8% and 14.8%; there were 6 sites mutations of HBV S gene at baseline were detected, and the frequency of S53L,T/I57S and N59H mutations were higher, respectively 48.1%,22.2% and 18.5%; there were 9 sites mutations of HBV X gene at baseline were detected, and the frequency of P42L and A44F/P/S mutations were higher, respectively 22.2% and 14.8%. (2) The following mutations were acompanied by the rtM204V/I±tL180M mutations, they were the HBV P gene mutations (rtP170T/G,rtA186D,rtR192D/P,rtR193G/K/M,rtS202N/R,rtF183S and T184A), BCP gene mutations (A1752G/T,T1753C,A1762T,G1764A,T1800C and A1814T), PC gene mutations (T1858C/A,G1896A and G1899A), C gene mutations (P5T/R,V13A,S26T/A,I27V,S35T,L60V,G63V,197L,P130T/H,P135Q/A,R157K/G and T147A), S gene mutations (P62L/Q,W74M and M75I), and X gene mutations (L37Q/V,S43A and A44F/P/S). (3) The following mutations were not acompanied by the rtM204V/I±rtL180M mutations, they were the HBV P gene mutations (rtA181V,rtM171R,rtN/H238T/A and rtI187V), BCP gene mutations (A1775G,C1799G and G1848A), PC gene mutations (C1856,G1862T and G1876T), C gene mutations (Y38H,A80S/G,Q99H and V149I), S gene mutations (S53L, Q56P,S61W,T63S,C69T,P70K and F83E), and X gene mutations (P33T/A,P40H,A36T and P38S)Conclusion:1 The following mutations at baseline may be predictors of HBV DNA rebound after lamividine treatment, they were the HBV P gene mutations (rtN/H238T/A,rtL217P/N and rtN248H), BCP gene mutations (A1762T,G1764A and A1775G), PC gene mutations (T1858C/A and G1896A), C gene mutations (P130T/H,L60V and S87G), S gene mutations (S53L,T/I57S and N59H), and X gene mutations (A44 F/P/S,S43A and P42L).2 The following mutations may be the compensation sites of the rtM204V/I±rtL180M mutations, they were the HBV P gene mutations (rtP170T/G,rtA186D,rtR192D/P,rtR193G/K/M,rtS202N/R,rtF183S and T184A), BCP gene mutations (A1752G/T,T1753C,A1762T,G1764A,T1800C and A1814T), PC gene mutations (T1858C/A,G1896A and G1899A), the HBV C gene mutations (P5T/R,V13A,S26T/A,I27V,S35T,L60V. G63V,I97L,P130T/H,P135Q/A,R157K/G and T147A), the HBV S gene mutations (P62L/Q,W74M and M75I), X gene mutations (L37Q/V,S43A and A44F/P/S).3 The following mutations may be the new mutation sites related to lamivudine-resistant, they were the HBV P gene mutations (rtA181V rtM171R,rtN/H238T/A and rtI187V), BCP gene mutations (A1775G,C1799G and G1848A), PC gene mutations (C1856T,G1862T and G1876T), C gene mutations (Y38H,A80S/G,Q99H and V149I), S gene mutations (S53L, Q56P,S61W,T63S,C69T,P70K and F83E), X gene mutations (P33T/A,P40H,A36T and P38S).