Relationship Between Single Nucleotide Polymorphism Of Programmed Cell Death 1 And Initial Virologic Response To Interferon-alpha In Patients With Chronic Hepatitis B

Background Antiviral therapy is the cure among all the therapies with chronic hepatitis B (CHB), Interferon-alpha?(IFN-α)?is?one?of?the?currently major?drugs?for?anti-HBV?treatment. However,?patients?react?differently to IFN-α?therapy. Studies indicated that ?the discrepancy ?of ?host, viral and environment may be included. In addition, host immunity genetic background may be one of the most important. This study aimed at investigating whether PD-1.1 and PD-1.2 genotype polymorphism of programmed cell death 1 (PD-1) is associated with the initial virologic response to IFN-αtherapy in Chinese Han patients with CHB, so it could improve the efficacy of IFN-αtherapy and make the treatment more rational or individual.Methods In our prospective study, we evaluated the initial virologic responses of 135 patients to IFN-αtherapy, and compared the therapeutic effect by classifying into three groups according to PD-1.1 and PD-1.2: AA, AG, and GG genotype groups. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to analyze the genotype polymorphism in PD-1.1 and PD-1.2 genotype.Results Among the 135 patients, 33(24.4%)had initial virologic response to IFN-α. 1. PD-1.1①No significant difference among the three genotypes was found in terms of the distribution of gender (χ~2=1.105, P=0.575), age (F=0.519, P=0.596), initial ALT level (F=0.187, P=0.829), pretreatment HBV DNA (F=0.759, P=0.470), and type of IFN-α(χ~2=0.058, P=0.971);②The respective frequencies of the initial virological response among the AA, AG and GG groups were 14.30%, 32.50% and 13.00%, respectively. The frequenciy of initial virological response among the AA, AG and GG genotype groups was significantly different(χ~2=6.258, P=0.044). However, no significant difference was found between the AA and GG groups (χ~2=0.018, P=0.893), the sample size of AA and GG groups is small, no difference was found between them (P=0.893), so Chi-square segmentation method was uesd, AA and GG groups are merged comparing with AG groups was significantly different (χ~2=6.246, P=0.012), so it could think the frequencies of initial virological response in the AG groups were higher than in the AA and GG group. 2. PD-1.2①No significant difference among the three genotypes was found in terms of the distribution of gender (χ~2=0.518, P=0.772), age (F=1.180, P=0.310), initial ALT level (F=1.892, P=0.155), pretreatment HBV DNA (F=1.442, P=0.240), and type of IFN-α(χ~2=0.331, P=0.848);②The respective frequencies of the initial virological response among the AA, AG and GG groups were 18.20%, 31.40% and 14.30%, respectively. No significant difference was found between the AA, AG and GG groups (χ~2=3.957, P=0.138).Conclusion SNPs of PD-1.1 as a potential marker could be used to predict the initial virologic response to IFN-αtreatment of Chinese Han patients with CHB, and expand the sample to be confirmed in the future.