Lam Yuk-Fai, Wong Danny Ka-Ho, Seto Wai-Kay, To Kelvin Kai-Wang, Hung Ivan Fan-Ngai, Fung James, Lai Ching-Lung, Yuen Man-Fung
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
J Gastroenterol Hepatol. 2014 Mar;29(3):533-9. doi: 10.1111/jgh.12378.
Studies show that polymorphisms in human leukocyte antigen (HLA)-DP loci and certain γ-interferon (IFN-γ) signaling pathway genes are related to persistence of hepatitis B virus (HBV) infection and viral load in chronic HBV (CHB) infection respectively. Our study aims to determine whether single-nucleotide polymorphisms (SNPs) linked to HLA-DP loci and IFN-γ signaling pathway are associated with HBV activities.
We compared the SNPs in the HLA-DPA1 gene (rs3077) and the IFN-γ receptor-2 gene (rs2284553 and rs9808753) of 100 treatment-naive hepatitis B e antigen (HBeAg)-negative CHB patients with undetectable HBV DNA with 100 age- and sex-matched controls with HBV DNA > 2000 IU/mL.
The median age of the study group was 47.9 years, and 61% were male patients. The distribution of the three polymorphisms was in Hardy-Weinberg equilibrium. Both rs3077 and rs2284553 polymorphisms were not associated with HBV viral load in terms of allelic frequency, genotypic frequency, dominant/recessive gene action. rs9808753 (G allele) was associated with a reduced chance of "undetectable HBV DNA" for patients below the age of 50 years in allelic frequency analysis (odds ratio 0.562; 95% confidence interval, 0.326-0.967; P value = 0.037). IFN-γ receptor-2 gene haplotype block (rs2284553/rs9808753) was not associated with HBV viral activity.
There was no significant association between HLA-DP polymorphism (rs3077) and IFN-γ receptor-2 gene polymorphism (rs2284553) with viral activity in HBeAg-negative CHB patients. Further studies are required to confirm the association between IFN-γ receptor-2 gene polymorphism (rs9808753) and reduced chance of having "undetectable HBV DNA" in young CHB patients.
研究表明，人类白细胞抗原（HLA）-DP基因座多态性和某些γ-干扰素（IFN-γ）信号通路基因分别与慢性乙型肝炎（CHB）感染中乙型肝炎病毒（HBV）感染的持续存在及病毒载量有关。本研究旨在确定与HLA-DP基因座及IFN-γ信号通路相关的单核苷酸多态性（SNP）是否与HBV活性相关。
我们将100例未经治疗、乙型肝炎e抗原（HBeAg）阴性、HBV DNA检测不到的CHB患者的HLA-DPA1基因（rs3077）及IFN-γ受体2基因（rs2284553和rs9808753）中的SNP与100例年龄及性别匹配、HBV DNA>2000 IU/mL的对照者进行了比较。
研究组的中位年龄为47.9岁，男性患者占61%。这三种多态性的分布符合Hardy-Weinberg平衡。就等位基因频率、基因型频率、显性/隐性基因作用而言，rs3077和rs2284553多态性均与HBV病毒载量无关。在等位基因频率分析中，rs9808753（G等位基因）与50岁以下患者“HBV DNA检测不到”的几率降低相关（比值比0.562；95%置信区间，0.326 - 0.967；P值 = 0.037）。IFN-γ受体2基因单倍型模块（rs2284553/rs9808753）与HBV病毒活性无关。
HBeAg阴性CHB患者中，HLA-DP多态性（rs3077）和IFN-γ受体2基因多态性（rs2284553）与病毒活性之间无显著关联。需要进一步研究以证实IFN-γ受体2基因多态性（rs9808753）与年轻CHB患者“HBV DNA检测不到”几率降低之间的关联。
