Li Wang-Xia, Xia Jia-An, Zhou Xia, Ma Yan, Shen Gang, Qiu Feng-Wu
HLA Typing Laboratory, Wuhan Blood Center, Wuhan, 430030, China.
Department of Neurology, Medical Treatment Center of Wuhan, Wuhan, 430024, China.
J Huazhong Univ Sci Technolog Med Sci. 2017 Feb;37(1):131-139. doi: 10.1007/s11596-017-1706-z. Epub 2017 Feb 22.
The HIV susceptibility and resistance alleles in the HLA genes were determined by investigating the distribution characteristics of the HLA alleles (A, B, and DRB1) in HIV-infected individuals of the Han population in Hubei, and by comparing these alleles with HIV-negative individuals from the same area. A cohort of 424 HIV-1 infected individuals were chosen as study subjects, and 836 HIV-negative healthy subjects from the same area served as the control population. HLA-A, B, and DRB1 allele typing was performed using polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) and polymerase chain reaction-sequencing based typing (PCR-SBT) techniques. Arlequin ver3.0 was used to analyze the allele and haplotype frequencies of HLA-A, B, and DRB 1, whereas Epi Info 7 and SPSS18.0 was used to analyze the differences in the HLA alleles between the HIV-1 positive and HIV-1 negative groups. A02:03, DRB101:01, and DRB115:01 alleles and their haplotypes as well as the HLA_Bw4-Bw6 hybrid showed a protective effect on HIV-1 infection. After adjusting for confounding factors such as age and sex, multivariate logistic regression analysis revealed that B15:02G, DRB101:01, and DRB115:01 subtypes were the resistance genes of HIV-1 infection, while B13:01 might increase susceptibility to HIV-1 infection. The correlation between A02:06 and B*15:01G subtypes and HIV-1 susceptibility was independent of the age and sex of the host. This study demonstrated the influence of genetic factors in humans such as HLA polymorphism on individuals to resist HIV-1 infection. Association studies of HLA polymorphism, susceptibility/resistance to HIV-1 infection, and hosts' genetic background are of significant importance for research on HIV-1 pathogenesis and vaccine design.
通过调查湖北汉族HIV感染者中HLA等位基因(A、B和DRB1)的分布特征,并将这些等位基因与来自同一地区的HIV阴性个体进行比较,来确定HLA基因中的HIV易感性和抗性等位基因。选择424名HIV-1感染者作为研究对象,来自同一地区的836名HIV阴性健康受试者作为对照人群。使用聚合酶链反应-序列特异性寡核苷酸探针(PCR-SSOP)和基于聚合酶链反应测序的分型(PCR-SBT)技术进行HLA-A、B和DRB1等位基因分型。使用Arlequin ver3.0分析HLA-A、B和DRB1的等位基因和单倍型频率,而使用Epi Info 7和SPSS18.0分析HIV-1阳性和HIV-1阴性组之间HLA等位基因的差异。A02:03、DRB101:01和DRB115:01等位基因及其单倍型以及HLA_Bw4-Bw6杂合体对HIV-1感染具有保护作用。在调整年龄和性别等混杂因素后,多因素逻辑回归分析显示B15:02G、DRB101:01和DRB115:01亚型是HIV-1感染的抗性基因,而B13:01可能增加对HIV-1感染的易感性。A02:06和B*15:01G亚型与HIV-1易感性之间的相关性独立于宿主的年龄和性别。本研究证明了人类遗传因素如HLA多态性对个体抵抗HIV-1感染的影响。HLA多态性、对HIV-1感染的易感性/抗性以及宿主遗传背景的关联研究对于HIV-1发病机制和疫苗设计的研究具有重要意义。