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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.
Objective: To investigate the relationship between YMDD mutation and allele frequencies of HLA-A, B and DRB1 loci in patients with chronic hepatitis B (CHB). Methods: 142 patients with CHB were enrolled in this study. The HBV YMDD mutation in plasma was detected by fluorescence-labeled hybridization double-probe PCR melting curve (FH-PCR-MC). The peripheral blood leukocytes of 56 patients were treated with sequence-specific primers / Human leukocyte surface antigen alleles (HLA-AB, DRB1) typing were detected by PCR-SSP. Results: Among 142 CHB patients treated with lamivudine, the YMDD mutation rate was 56.3%. The frequencies of HLA-B * 58 and DRB1 * 03 alleles were significantly lower in the YMDD mutation group than in the wild-type YMDD group (0.013 vs 0.094, P = 0.036; 063, P = 0.024). The distribution of HLA-A * 30 alleles in YIDD group was significantly higher than that in YVDD group (0.158 vs 0.024, P = 0.034) The distribution frequency of A ~ * 33 allele in YVDD mutation group was significantly higher than that in YIDD mutation group (0.119 vs 0.000, P = 0.028). Conclusion: The resistance variation of YMDD has some correlation with HLA allele polymorphism. HBV infected with individuals with HLA-B * * 58 and DRB1 * * 03 alleles may not be susceptible to YMDD mutation; individuals infected with HLA-A * 30 alleles may be susceptible to YIDD mutations: Individuals infected with the HLA-A * 33 allele may be susceptible to YVDD mutations.