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目的调查HIV感染者的HLA-A,B,DRB1等位基因的分布特征,并与具有同样高危行为的HIV阴性者相比较,拟发现在HLA基因中HIV-1感染的易感和抗性基因。方法将712名HIV-1感染者作为研究对象,以358名高危行为HIV阴性者为对照,采用基于Luminex流式荧光分析仪的PCR-SSO方法进行HLA-A、B和DRB1等位基因的基因分型。使用Arlequinver2.000软件分析两组HLA-A,B,DRB1等位基因和单体型的频率,使用EpiInfo2002软件和SPSS14.0软件分析HIV-1阳性组和HIV阴性组的HLA等位基因的差异。结果本研究获得了重庆地区汉族HIV-1感染者和高危行为HIV阴性者的HLA-A,B,DRB1基因亚型的分布情况和单体型的组成情况。以具有同样高危行为的HIV阴性者做对照进行病例对照的HLA基因亚型与HIV-1感染者的关联研究,结果显示携带B*3901和B*5101等位基因及其组成的单体型和HLA_Bw4-Bw6杂合体对HIV-1感染有保护作用。HLA-Ⅱ类基因的DRB1*0403和DRB1*1101的基因可能会增加HIV-1感染的危险性,通过调整年龄和性别混杂因素后的多因素Logistic回归分析显示,以上HLA等位基因亚型与HIV-1感染的相关性独立于宿主年龄和性别的影响作用。另外携带B*40等位基因及其组成的单体型可能会增加HIV-1感染的危险性,而A*0101-B*3701和A*0101-B*3701-DRB1*1001单体型和该人群中常见单体型也可能是HIV-1感染的危险因素。结论此研究推证了人类自身遗传因素中HLA基因多态性影响个体抵抗HIV-1感染的能力。该人群的HLA等位基因多态性分析和HIV-1感染的易感性/抗性与宿主遗传背景HLA的关联研究对于HIV感染和致病机制的研究和HIV疫苗设计有着重要意义。
Objective To investigate the distribution of HLA-A, B and DRB1 alleles in HIV-infected individuals and to identify the susceptible and resistant genes of HIV-1 infection in HLA genes compared with those of HIV-negative individuals with the same high-risk behaviors . Methods A total of 712 HIV-1 infected patients were enrolled in this study. 358 high-risk HIV-negative individuals were used as controls. The genes of HLA-A, B and DRB1 alleles were analyzed by PCR-SSO based on Luminex flow cytometry Type. The frequency of HLA-A, B, DRB1 alleles and haplotypes was analyzed using Arlequinver2.000 software. The differences of HLA alleles between HIV-1 positive and HIV negative groups were analyzed using EpiInfo2002 software and SPSS14.0 software . Results The distribution of HLA-A, B and DRB1 genotypes and haplotype composition of HIV-1-infected and HIV-negative individuals in Han nationality in Chongqing were obtained. A case-control study of association between HLA subtypes and HIV-1 in HIV-negative women with similar high-risk behaviors was performed. The results showed that haplotypes carrying B * 3901 and B * 5101 alleles and their haplotype HLA_Bw4-Bw6 hybrids have a protective effect against HIV-1 infection. HLA-Ⅱ DRB1 * 0403 and DRB1 * 1101 genes may increase the risk of HIV-1 infection by adjusting age and gender confounders multivariate logistic regression analysis showed that the above HLA alleles and The relevance of HIV-1 infection is independent of the age and sex of the host. In addition, haplotypes carrying the B * 40 allele and its composition may increase the risk of HIV-1 infection, whereas A * 0101-B * 3701 and A * 0101-B * 3701-DRB1 * Common haplotypes in this population may also be risk factors for HIV-1 infection. Conclusions This study demonstrates that HLA polymorphism in human genetic factors affects individuals’ ability to fight HIV-1 infection. The HLA allele polymorphism analysis of this population and the association of susceptibility / resistance of HIV-1 infection with host genetic background HLA have important implications for the study of HIV infection and pathogenesis and HIV vaccine design.