拉米夫定治疗慢性乙型肝炎预后与 HLA-DQ 基因多态性的分析

摘要

Objective To study the relevance of two single-nucleotide polymorphisms (HLA-DQ rs28567185 and rs9275572)with different prognosis to lamivudine therapy for chronic hepatitis B.Methods A total of 283 samples were enrolled,and peripheral blood samples were collected in this study.The single-nucleotide polymorphisms in the HLA-DQ region were genotyped using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Logistic regression was applied to case-control comparisons for the different phenotypic outcomes in co-dominant,dominant and recessive genetic models,adjusted for sex and age.Results The study demonstrated the clear relevance of HLA-DQ rs2856718 and rs9275572 with DNA response and ALT response.HLA-DQ rs2856718G and rs9275572A were strongly associated with increased risk of ALT response (OR = 1.732;P = 0.034;OR = 2.846,P < 0.001).Moreover,rs9275572A was also associated with increased risk of DNA response (OR =2.387,P =0.007).Conclusion Our study suggested that HLA-DQ loci were associated with the different prognosis to lamivudine therapy in Han Chinese,rs2856718G and rs9275572A were protective factors for ALT response and DNA response.%目的：探讨 HLA-DQ 基因 rs2856718和 rs927557的2个位点突变是否与拉米夫定（lamivudine， LAM）治疗慢性乙型肝炎预后有关。方法采用调查问卷收集283例研究对象的一般资料，同时收集其外周血，提取 DNA，用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF MS）实验平台进行 DNA 的 SNPs 分型，使用单因素及多因素 Logistic 回归方法分析 HLA-DQ 基因多态性与 LAM 治疗慢性乙型肝炎预后不同结局的关系。结果携带 HLA-DQ 基因 rs2856718G 和 rs9275572A 的个体 ALT 应答的可能性增加（OR ＝1.732，P ＝0.034；OR ＝2.846，P ＜0.001）。另外，携带 rs9275572A 的个体 DNA 应答的可能性也增加（OR ＝2.387，P ＝0.007）。结论在中国北方汉族人群中，HLA-DQ 的2个 SNP 位点（rs9275572和 rs2856718）与 LAM 治疗慢性乙型肝炎预后有关， rs9275572A 和 rs2856718G 为 ALT 应答和 DNA 应答的保护性因素。