HBV感染者人类白细胞Ⅰ,Ⅱ类抗原等位基因多态性分析

Analysis of polymorphism of human leukocyte antigen Class Ⅰ and Ⅱ alleles in patients with hepatitis B virus infection

目的:分析HBV感染者体内病毒持续和清除与HLA-A,B,DRB1各位点等位基因分布频率的关系.方法:采用序列特异性引物-聚合酶链式反应(PCR-SSP)技术,对61例慢性乙型肝炎患者(CHB)、32例HBV感染后病毒清除者(感染恢复组)和40例骨髓移植供者(正常组)的外周血白细胞,进行人类白细胞抗原等位基因(HLA-A,B,DRB1)分型检测.结果:在慢性乙型肝炎组,HLA-DRB1*12等位基因分布频率较正常组(0.230vs0.075,P=0.004,OR=3.674,95%CI:1.445-9.338)和HBV感染恢复组(0.230vs0.063,P=0.004,OR=4.468,95%CI:1.492-13.377)均显著增高,HLA-B*35,DRB1*13则显著降低(0.066vs0.163,P=0.027,OR=0.362,95%CI:0.143-0.918;0.016vs0.008,P=0.017,OR=0.174,95%CI:0.035-0.859);HLA-A*69,B*56也显著降低(均0.000vs0.037,P=0.031).HLA-A*02等位基因分布频率在慢性肝炎组与HBV感染恢复组比较显著降低(P=0.044),HLA-B*51在感染恢复组与正常组比较显著增高(P=0.019).结论:机体对HBV易感性和病毒持续或清除与HLA等位基因多态性相关.HLA-DRB1*12可能既为易感性位点,又能促进病毒的持续感染;HLA-B*51,A*02可能为易感性位点,但感染后易清除病毒;HLA-DRB1*13可能是抗HBV感染的保护性基因;HLA-B*35,B*56和A*69在中国北方汉族人可能也为抗HBV感染的保护性基因.

AIM： To investigate the polymorphism of human leukocyte antigen （HLA） Class I and II alleles in patients with hepatitis B virus （HBV） infection, and to explore the correlations of HBV infection with HLA-A, B, DRB1 aUelic frequencies. METHODS： The polymerase chain reaction-sequence-specific primer （PCR-SSP） technique was used to determine the frequencies of HLA-A, B, DRB1 alleles in 61 patients with chronic hepatitis B （CHB）, 30 recovered people from HBV infection and 40 healthy bone marrow donors （normal controls） in Heilongjiang province.RESULTS： The allelic frequencies of HLA- DRB1^＊12 in CHB patients were markedly higher than those in the normal controls and recovered patients （0.230 vs 0.075, P = 0.004, OR = 3.674, 95%CI： 1.445-9.338; 0.230 vs 0.063, P = 0.004, OR = 4.468, 95%CI： 1.492-13.377）, but the aUelic frequencies of HLA-B^＊35 and DRB1^＊13 were markedly lower （0.066 vs 0.163, P = 0.027, OR = 0.362, 95%CI： 0.143-0.918; 0.016 vs 0.008, P - 0.017, OR = 0.174, 95%CI： 0.035-0.859）. The allele frequencies of HLA-B＊51 and A^＊02 in the recovered patients were significantly higher than those in the normal controls （0.125 vs 0.025, P = 0.019, OR = 5.587, 95%CI： 1.139-27.027） and CHB patients （0.221 vs 0.360, P = 0.044, OR = 0.507, 95%CI： 0.260-0.986）, respectively. The frequencies of HLA-A^＊69 and B^＊56 were markedly lower in the CHB patients than those in the normal controls （0.000 vs 0.037, P = 0.031; 0.000 vs 0.037, P = 0.031）. The allelic frequency of HLA-A^＊02 was significantly higher in CHB patients than that in the recovered patients （P = 0.044）, and the frequency of HLA-B^＊51 was markedly higher in the recovered patients than that in the controls （P = 0.019）. CONCLUSION： HLA-DRB1^＊12 is highly associated with the susceptibility of patients to HBV infection and viral persistence. HLA-B^＊51 and A^＊02 are closely associated with the susceptibility to HBV infection and viral clearance. HLA-B^＊35, DRB1^＊13, B^＊56 and A^＊69 are associated with the protection against HBV infection.