陕西汉族人群人类白细胞抗原多态性与隐匿性乙型肝炎病毒感染的关系。

Association of human leukocyte antigen polymorphisms with occult hepatitis B virus infection in a Shaanxi Han population.

机构信息

Department of Immunology and Pathogenic Biology, School of Basic Medical Sciences, Xi'an Jiaotong University Health Science Center, Xi'an, Shaanxi, People's Republic of China.

Blood Center of the Shaanxi Province, Xi'an, Shaanxi, People's Republic of China.

出版信息

J Gene Med. 2017 Sep;19(9-10). doi: 10.1002/jgm.2987. Epub 2017 Oct 18.

DOI:10.1002/jgm.2987

PMID:28940887

Abstract

BACKGROUND

Occult hepatitis B virus (HBV) infection (OBI) is defined as HBV DNA detection in serum or in the liver by sensitive diagnostic tests in HBV surface antigen (HBsAg) negative patients with or without serologic markers of previous HBV exposure. Because the human leukocyte antigen (HLA) system is an integral component of the immune response, we hypothesized that the highly polymorphic HLA genes were the key determinants of HBV persistence and clearance. The present study aimed to calculate the allelic frequency of HLA loci and investigate the association between HLA alleles and the outcome of OBI in Shaanxi Han population in the northwest of China.

METHODS

We conducted a case-control study between 107 OBI subjects and 280 healthy control individuals from blood donors of Shaanxi Blood Center. Five HLA loci, including HLA-A,-B,-C,-DRB1 and -DQB1, were selected and further genotyped using a polymerase chain reaction sequence-based typing (SBT) method.

RESULTS

Using the chi-squared test, we found that the allele frequencies of HLA-B44:03 [odds ratios (OR) = 2.146, 95% confidence interval (CI) = 1.070-4.306, p = 0.028]; C07:01 (OR = 4.693, CI = 1.822-12.086, p = 0.000); DQB102:02 (OR = 1.919, CI = 1.188-3.101, p = 0.007); and DRB107:01 (OR = 2.012, CI = 1.303-3.107, p = 0.001) were markedly higher in the OBI group compared to the healthy control group. The allele frequencies of HLA-DRB108:03 (OR = 0.395, CI = 0.152-1.027, p = 0.049); DRB115:01 (OR = 0.495, CI = 0.261-0.940, p = 0.029); and DQB106:02 (OR = 0.500, CI = 0.249-1.005, p = 0.048) were obviously lower in the OBI group compared to the healthy control group. These data indicated that HLA-B44:03, C07:01, DQB102:02 and DRB107:01 were related to OBI infection, whereas HLA-DRB108:03, DRB115:01 and DQB106:02 alleles were associated with HBV DNA clearance in a Shaanxi Han population.

CONCLUSIONS

The results of the present study suggest that host HLA gene is an important influencing factor for OBI pathogenesis.

摘要

背景

隐匿性乙型肝炎病毒（HBV）感染（OBI）定义为在 HBV 表面抗原（HBsAg）阴性的患者中，通过敏感的诊断检测在血清或肝脏中检测到 HBV DNA，无论其是否存在 HBV 既往暴露的血清学标志物。由于人类白细胞抗原（HLA）系统是免疫反应的一个组成部分，我们假设高度多态性的 HLA 基因是 HBV 持续存在和清除的关键决定因素。本研究旨在计算 HLA 基因座的等位基因频率，并探讨 HLA 等位基因与中国西北部陕西汉族人群 OBI 结局之间的关系。

方法

我们进行了一项病例对照研究，比较了 107 例 OBI 患者和 280 名来自陕西血液中心献血者的健康对照者。选择了五个 HLA 基因座，包括 HLA-A、-B、-C、-DRB1 和 -DQB1，并使用聚合酶链反应序列基础分型（SBT）方法进一步进行基因分型。

结果

使用卡方检验，我们发现 HLA-B44:03 的等位基因频率[比值比（OR）=2.146，95%置信区间（CI）=1.070-4.306，p=0.028]；C07:01（OR=4.693，CI=1.822-12.086，p=0.000）；DQB102:02（OR=1.919，CI=1.188-3.101，p=0.007）；和 DRB107:01（OR=2.012，CI=1.303-3.107，p=0.001）在 OBI 组中明显高于健康对照组。HLA-DRB108:03 的等位基因频率[比值比（OR）=0.395，CI=0.152-1.027，p=0.049]；DRB115:01（OR=0.495，CI=0.261-0.940，p=0.029）；和 DQB106:02（OR=0.500，CI=0.249-1.005，p=0.048）在 OBI 组中明显低于健康对照组。这些数据表明，HLA-B44:03、C07:01、DQB102:02 和 DRB107:01 与 OBI 感染有关，而 HLA-DRB108:03、DRB115:01 和 DQB106:02 等位基因与 HBV DNA 清除有关。