Human Leukocyte Antigen(HLA)-DRB1 Polymorphism Is Associated With Familial Hepatitis B In Shanxi

Objective (1)To assess the associations of human leukocyte antigen (HLA)-DRB1 polymorphism with the outcome of familial hepatitis B and the replication of hepatitis B virus in shanxi.(2)To study the association between human leukocyte antigen (HLA)-DRB1 polymorphism and short term antiviral efficacy of adefovir(ADV).Methods (1)The patients and their lineal consanguinity(295) from hepatitis B families were divided into the healthy control (CON)group, chronic asymptomatic carrier(ASC) group, chronic hepatitis B(CHB) group and liver cirrhosis (LC) group. The frequencies of HLA-DRB1 among the groups and among different replication of HBV were analyzed by PCR-SSOP and flow PRATW beads. (2) HBV genotype was analyzed by nest polymerase chain reaction-restriction fragment length polymorph-ism (ntPCR-RFLP).We divided the patients who take in adefovir and carry genotype C of HBV into the effctive group and the ineffctive group, and analyzed the frequencies of HLA-DRB1 between the two groups.Results (1)The frequencies of HLA-DRB1*04 in the CON group was 15.9%,which was higher than those in ASC group (6.9%) and CHB group (7.9%),and the differen-ces were of statistical significance (χ2=4.892 and 4.072, P<0.05).The frequencies of HLA-DRB1*07 in CHB group and LC group were 13.1% and 15.4%,significantly higher than that in the CON group(4.9%,χ2=4.140 and 5.529,P<0.05).The frequency of HLA-DRB1*13 in the CON group was 3.7%,which was higher than that in the CHB group (0%,χ2=3.316,P<0.05).The frequencies of HLA-DRB1*15 in ASC group and LC group were 20.6% and 11.5%,the difference between the two groups was of statistical significance (χ2=4.287,P<0.05).The frequencies of other DRB1 alleles were not significantly different among the groups.Significant difference on the average ages was observed among ASC,CHB and LC groups (F=33.38, P<0.01), the paired comparison of ASC and CHB with LC groupshowed markedly significant difference (t=-8.931,-6.208, P<0.05).The frequencies of HLA-DRB1*07 were significantly higher in the HBV-DNA positive group than that in the HBV-DNA negative group (16.7% vs 9.6%,,χ2=5.268, P<0.01), the differences were of statistical significance. (2)The frequency of HLA-DRB 1*04 was higher in the effctive group (18.3%) than that in the ineffective group(3.9%),and the frequency of HLA-DRB1*07 was lower in the effctive group (1.7%) than that in the inefffective group (15.4%), the differen-ces were of statistical significance.The frequencies of other DRB1 alleles were not significantly different between the two groups.Conclusion (1)HLA-DRB1*07 allele is associated with the susceptibility to familial hepatitis B,which may be the susceptibility gene or linked gene for familial hepatitis B in Shanxi, The age(the time of HBV infection and the course of disease) may play a role in the clinical outcome of HBV infection.HLA-DRB1*07 allele is markedly high-er in the replication of HBV;HLA-DRB1*04 and HLA-DRB1*13 are associated with the resistance to familial hepatitis B,which may be the resistant genes for familial hepatitis B in Shanxi.(2)HLA-DRB1*04 may predict that the one who carry HLA-DRB1*04 and carry genotype C of HBV is likely to have a good response to adefovir, HLA-DRB 1*07 may predict to have a bad response to adefovir.