YMDD耐药变异与HLA等位基因多态性的相关性

目的：初步探讨慢性乙型肝炎(CHB)患者拉米夫定治疗中YMDD变异与HLA-A,B,DRB1各位点等位基因分布频率的相关性．方法：对142例CHB患者,采用荧光标记杂交双探针PCR融解曲线法(FH-PCR-MC)检测血浆HBV YMDD变异；对其中56例患者的外周血白细胞,采用序列特异性引物/聚合酶链式反应(PCR-SSP)技术检测人类白细胞表面抗原等位基因(HLA-A-B,DRB1)分型．结果：在用拉米夫定治疗的142例CHB患者中,YMDD变异率为56．3％．HLA-B~*58和DRB1~*03等位基因分布频率在YMDD变异组与YMDD野生组比较有显著性降低(0．013 vs 0．094,P=0．036；0．000 vs 0．063,P=0．024)；HLA-A~*30等位基因分布频率在YIDD组明显增高,与YVDD组比较差异显著(0．158 vs 0．024,P=0．034)；HLA-A~*33等位基因分布频率在YVDD变异组明显增高,与YIDD变异组比较差异显著(0．119 vs 0．000,P=0．028)．结论：YMDD耐药变异与HLA等位基因多态性有一定相关性．携有HLA-B~*58和DRB1~*03等位基因的个体感染的HBV可能不易发生YMDD变异；携有HLA-A~*30等位基因的个体感染的HBV可能易发生YIDD变异：携有HLA-A~*33等位基因的个体感染的HBV可能易发生YVDD变异．

Correlation of hepatitis B virus YMDD mutations with the polymorphism of HLA alleles in patients with chronic hepatitis B virus infection

AIM:To investigate the relationship between HBV YMDD mutations and the polymorphism of human leukocyte antigen(HLA)alleles in patients with chronic hepatitis B virus(HBV) infection. METHODS:Fluorescent hybridization biprobe PCR and melting curve assay(FH-PCR-MC)was used to determine HBV YMDD mutations in serum specimens from 142 patients with chronic HBV infection.HLA-A,B,and DRB1 alleles in peripheral blood mononuclear cells(PBMCs) were detected by polymerase chain reaction- sequence specific primer(PCR-SSP).The PBMCs were collected from 56 of the 142 patients. RESULTS:YMDD mutations occurred in 56.3% of the 142 patients who received lumivudine treatment.The frequencies of HLA-B*58 and DRB1*03 alleles were significantly lower in YMDD mutation group in comparison with those in YMDD wild group(0.013 vs 0.094,P= 0.036;0.000 vs 0.063,P=0.024).The frequency of HLA-A*30 allele was markedly higher in YIDD group than that in YVDD group(0.158 vs 0.024, P=0.034),while the frequency of HLA-A*33 al- lele was lower in YIDD group(0.119 vs 0.000,P= 0.028). CONCLUSION:YMDD mutation is associ- ated with the polymorphism of HLA alleles in patients with chronic hepatitis B.Individuals with HLA-B~*58 and DRBI~*03 alleles may have resistance to YMDD mutation.Patients with HLA-A~*30 allele may have a susceptibility to YIDD mutation,and those with HLA-A~*33 al- lele are susceptible to YVDD mutation.