Tag SNP Host Genetic Correlation Analysis In CHB Patients With Different Responses To Antiviral Therapy

Objective IL-12 A, IL-1B and IL-17 A play important roles in immune response to HBV. The study aimed to observe the association between IL-12 A, IL-1B and IL-17 A gene polymorphisms and HBe Ag seroconversion in chronic hepatitis B patients who received nucleotide analogues treatment through case- control genetic association studies.Methods The study included 109 HBe Ag-positive chronic hepatitis B patients who had received entecavir treatment. The HBe Ag loss, HBe Ag seroconversion, HBV DNA levels decline> 103IU/L, ALT normalization were used to assess the response at 24 month, in which HBe Ag loss occurred in 33 cases, 76 cases remained positive; 29 cases reached HBe Ag seroconversion; 52 cases had HBV DNA levels decline > 103 IU/L; 27 cases obtained ALT normalization. The study included 179 HBe Ag-positive chronic hepatitis B patients who had received nucleotide analogues treatment. in which HBe Ag loss occurred in 55 cases, 124 cases remained positive; 46 cases reached HBe Ag seroconversion; 121 cases had HBV DNA levels decline > 103 IU/L; 114 cases obtained ALT normalization. The association between the IL-12 A rs568408, IL-1B rs1143623, IL-17 A rs8193036, HLA-DP rs3077 、 HLA-DP rs9277535 、 HLA-DQrs7453920 and HLA-DQrs2856718 genotype and HBe Ag loss, HBe Ag seroconversion, HBV DNA levels decline> 103 IU/L and ALT normalization were analysed.Results 1. IL-12 A rs568408 was associated with HBe Ag loss and HBe Ag seroconversion [OR=0.31(0.11-0.91),P=0.031;OR=3.72(1.34-10.32),P=0.012].GA genotype achieved higher HBe Ag loss and HBe Ag seroconversion rate than GG genotype. However, there was no significant association between HBV DNA levels decline>103IU/L[OR=1.27(0.45-3.50)P=0.65]and ALT normalization[OR=1.27(0.45-3.50),P=0.65].2. IL-1B rs1143623 and HBV DNA levels decline> 103 IU/L had a significant correlation, GG genotype was significantly higher than C/C –C/G genotype [OR = 4.47(1.35-14.84), P = 0.01]. No significant association between IL-1B rs1143623 and HBe Ag loss [OR = 10.55(0.17-1.77, P = 0.32], HBe Ag seroconversion [OR = 1.99(0.72- 5.44), P = 0.17], ALT normalization [OR = 10.52( 0.13-1.97), P = 0.31] was observed.3. No significant association between IL-17 A rs8193036 and HBe Ag loss [OR = 1.54(0.32-7.33), P = 0.60], HBe Ag seroconversion [OR = 1.54(0.32-7.33),P = 0.60], HBV DNA levels decline > 103 [OR = 0.61(0.25-1.47), P = 0.41], ALT normalization [OR =1.55(0.33-7.19),P=0.58] was observed.4. No significant association between HLA-DP rs3077, rs9277535, HLA-DQ rs7453920, rs2856718 and HBe Ag loss, HBe Ag seroconversion, HBV DNA levels decline > 103, ALT normalization was observed.Conclusion 1. IL-12 A rs568408 may correlate to HBe Ag loss or HBe Ag seroconversion. Patients with genotype GA are more likely to obtain HBe Ag loss or HBe Ag serum conversion than those with genotype GG after treated with ETV.2. IL-1B rs1143623 may correlate to serum HBV DNA clearance. Patients with genotype GG are more likely to decrease serum HBV DNA level than those with genotype CC/CG after treated with ETV.3. IL-17 A rs8193036 may not influence the outcome of patients treated with ETV. 4. HLA-DP rs3077、HLA-DP rs9277535、HLA-DQrs7453920 and HLA-DQ rs2856718 may be irrelevant to the outcome of patients treated with nucleotide analogues.