The Case-control Study Of -HLADRB1*0701, HLA-DQB1*0201, Environmental Risk Factor And Non-or Hyporesponsse To Hepatitis B Vaccine

Objective: To primarily confirm the association of HLA-DRB1*0701, HLA-DQB1*0201, and environmenmtal factor such as smoking, drinking etc. independently and in combination with the non-or hyporesponsse to hepatitis B vaccine.Methods: A case-control study which included 128 non-or hyporesponders and 128 responders from 1342 healthy adults who were subjected to a standard course of immunization with recombinant hepatitits B virus vaccine. All subjects were investigated with a uniform questionnaire. HLA-DRB1*0701 and HLA-DQB1*0201 genes were detected with ploymerse chain reaction-sequence specific primes(PCR-SSP). The data were analysed by SPSS 13.0 software.Results: (1)Univariate analysis indicated that age(OR=2.52,95%CI 1.51～4.21),BMI(OR=2.38,95%CI 1.13～5.02),smoking(OR=2.15,95%CI 1.08～4.28) and tea(OR=0.32,95%CI 0.10～0.99)(OR=0.32,95%CI 0.10～0.99) were associated with non-or hyporesponse.(2)The DRB1*0701 allele was found at a frequency of 16.4% in the non-or hyporesponders which was significant when compared with the responders(3.9%,χ2=10.959,P=0.002,OR=4.83). The DQB1*0201 allele was found at a frequency of 29.7% in the non-or hyporesponders which was significant when compared with the responders(14.1%,χ2=9.143,P=0.002,OR=2.58).The results showed that a combination of two gene was strongly associated with non-or hyporesponse. Carried the DRB1*0701 and DQB1*0201 in the non-or hyporesponders which was significant when compared with didn't carry genes in the responders(χ2 = 11.100, P = 0.001, OR=5.63). (3) The results of multivariate logistic regression showed that only 3 factors were entered in the model. They included age ( OR=2.12,95%CI 1.24～3.63 ) , BMI(OR=2.21,95%CI 1.04～4.72),DRB1*0701(OR=4.08,95%CI 1.45～11.46). (3) Interaction analysis suggested that there was synergistic interaction between age and gene, and also between BMI and gene. Interaction of the HLA-DRB1*0701 with smoking on non-or hyporesponse appearing a multiplicative model. Interaction of the DRB1*0701 with age to start smoking showed a low exposure-gene(LEG) effect on non-or hyporesponse,and that of the DRB1*0701 and smoked years or smoked per day showed a high exposure-gene(HEG)effect. Interaction of the HLA-DQB1*0201 with smoking on non-or hyporesponse appearing a multiplicative model. Interaction of the D1Q1*07201 with age to start smoking showed a low exposure-gene(LEG) effect on non-or hyporesponse.Conclusion: Many factors were associated with non-or hyporesponse. The interaction were between gene and environmental. Mechanisms for interactions of different environmental factors varied with the same genotype or with different genotypes, suggesting that genetic- environmental interaction was not simply gene- or environment-specific. Therefore, it is very important to consider the genetic-environmental interaction for non-or hyporesponse.