Al-Qahtani Ahmed A, Al-Anazi Mashael R, Abdo Ayman A, Sanai Faisal M, Al-Hamoudi Waleed, Alswat Khalid A, Al-Ashgar Hamad I, Khalaf Nisreen Z, Eldali Abdelmoneim M, Viswan Nisha A, Al-Ahdal Mohammed N
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia ; Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia.
Department of Infection and Immunity, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia.
PLoS One. 2014 Jan 22;9(1):e80445. doi: 10.1371/journal.pone.0080445. eCollection 2014.
Hepatitis B virus (HBV) infection is a leading cause of liver diseases including cirrhosis and hepatocellular carcinoma. Human leukocyte antigens (HLAs) play an important role in the regulation of immune response against infectious organisms, including HBV. Recently, several genome-wide association (GWAS) studies have shown that genetic variations in HLA genes influence disease progression in HBV infection. The aim of this study was to investigate the role of HLA genetic polymorphisms and their possible role in HBV infection in Saudi Arabian patients. Variations in HLA genes were screened in 1672 subjects who were divided according to their clinical status into six categories as follows; clearance group, inactive carriers, active carriers, cirrhosis, hepatocellular carcinoma (HCC) patients and uninfected healthy controls. Three single nucleotide polymorphisms (SNPs) belonged to HLA-DQ region (rs2856718, rs7453920 and rs9275572) and two SNPs belonged to HLA-DP (rs3077 and rs9277535) were studied. The SNPs were genotyped by PCR-based DNA sequencing (rs2856718) and allele specific TaqMan genotyping assays (rs3077, rs7453920, rs9277535 and rs9275572). The results showed that rs2856718, rs3077, rs9277535 and rs9275572 were associated with HBV infection (p = 0.0003, OR = 1.351, CI = 1.147-1.591; p = 0.041, OR = 1.20, CI = 1.007-1.43; p = 0.045, OR = 1.198, CI = 1.004-1.43 and p = 0.0018, OR = 0.776, CI = 0.662-0.910, respectively). However, allele frequency of rs2856718, rs7453920 and rs9275572 were found more in chronically infected patients when compared to clearance group infection (p = 0.0001, OR = 1.462, CI = 1.204-1.776; p = 0.0178, OR = 1.267, CI = 1.042-1.540 and p = 0.010, OR = 0.776, CI = 0.639-0.942, respectively). No association was found when polymorphisms in HLA genes were compared in active carriers versus cirrhosis/HCC patients. In conclusion, these results suggest that variations in HLA genes could affect susceptibility to and clearance of HBV infection in Saudi Arabian patients.
乙型肝炎病毒（HBV）感染是包括肝硬化和肝细胞癌在内的肝脏疾病的主要病因。人类白细胞抗原（HLA）在调节针对包括HBV在内的感染性生物体的免疫反应中发挥重要作用。最近，几项全基因组关联（GWAS）研究表明，HLA基因的遗传变异会影响HBV感染的疾病进展。本研究的目的是调查HLA基因多态性在沙特阿拉伯患者HBV感染中的作用及其可能发挥的作用。对1672名受试者的HLA基因变异进行了筛查，这些受试者根据临床状态分为以下六类：清除组、非活动性携带者、活动性携带者、肝硬化、肝细胞癌（HCC）患者和未感染的健康对照。研究了属于HLA-DQ区域的三个单核苷酸多态性（SNP）（rs2856718、rs7453920和rs9275572）以及属于HLA-DP的两个SNP（rs3077和rs9277535）。通过基于PCR的DNA测序（rs2856718）和等位基因特异性TaqMan基因分型检测（rs3077、rs7453920、rs9277535和rs9275572）对这些SNP进行基因分型。结果显示，rs2856718、rs3077、rs9277535和rs9275572与HBV感染相关（p = 0.0003，OR = 1.351，CI = 1.147 - 1.591；p = 0.041，OR = 1.20，CI = 1.007 - 1.43；p = 0.045，OR = 1.198，CI = 1.004 - 1.43；p = 0.0018，OR = 0.776，CI = 0.662 - 0.910）。然而，与清除组感染相比，慢性感染患者中rs2856718、rs7453920和rs9275572的等位基因频率更高（p = 0.0001，OR = 1.462，CI = 1.204 - 1.776；p = 0.0178，OR = 1.267，CI = 1.042 - 1.540；p = 0.010，OR = 0.776，CI = 0.639 - 0.942）。在活动性携带者与肝硬化/HCC患者中比较HLA基因多态性时未发现关联。总之，这些结果表明，HLA基因变异可能影响沙特阿拉伯患者对HBV感染的易感性和清除能力。
