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中国重庆人群 HLA-A、B、DRB1 等位基因及单体型与 HIV-1 感染的相关性研究。

Association of HLA-A, B, DRB1 alleles and haplotypes with HIV-1 infection in Chongqing, China.

机构信息

Department of Epidemiology, Third Military Medical University, Chongqing, PR China.

出版信息

BMC Infect Dis. 2009 Dec 12;9:201. doi: 10.1186/1471-2334-9-201.

Abstract

BACKGROUND

The human immunodeficiency virus type 1(HIV-1) epidemic in Chongqing, China, is increasing rapidly with the dominant subtype of CRF07_BC over the past 3 years. Since human leukocyte antigen (HLA) polymorphisms have shown strong association with susceptibility/resistance to HIV-1 infection from individuals with different ethnic backgrounds, a recent investigation on frequencies of HLA class I and class II alleles in a Chinese cohort also indicated that similar correlation existed in HIV infected individuals from several provinces in China, however, such information is unavailable in Chongqing, southwest China.

METHODS

In this population-based study, we performed polymerase chain reaction analysis with sequence-specific oligonucleotide probes (PCR-SSOP) for intermediate-low-resolution HLA typing in a cohort of 549 HIV-1 infected individuals, another 2475 healthy subjects from the Han nationality in Chongqing, China, were selected as population control. We compared frequencies of HLA-A, B, DRB1 alleles, haplotypes and genotypes between the two groups, and analyzed their association with HIV-1 susceptibility or resistance.

RESULTS

The genetic profile of HLA (A, B, DRB1) alleles of HIV-1 infected individuals from Chongqing Han of China was obtained. Several alleles of HLA-B such as B46 (P = 0.001, OR = 1.38, 95%CI = 1.13-1.68), B1501G(B62) (P = 0.013, OR = 1.42, 95%CI = 1.08-1.88), B67 (P = 0.022, OR = 2.76, 95%CI = 1.16-6.57), B37 (P = 0.014, OR = 1.93, 95%CI = 1.14-3.28) and B52 (P = 0.038, OR = 1.64, 95%CI = 1.03-2.61) were observed to have association with susceptibility to HIV-1 infection in this population. In addition, the haplotype analysis revealed that A11-B46, A24-B54 and A01-B37 for 2-locus, and A11-B46-DRB109, A02-B46-DRB108, A11-B4001G-DRB115, A02-B4001G-DRB104, A11-B46-DRB108 and A02-B4001G-DRB112 for 3-locus had significantly overrepresented in HIV-1 infected individuals, whereas A11-B1502G, A11-B1502G-DRB112 and A33-B58-DRB1*13 were underrepresented. However, the low-resolution homozygosity of HLA-A, B, DRB1 loci and HLA-Bw4/Bw6 genotypes did not differ significantly between the two groups.

CONCLUSION

These results may contribute to the database of HLA profiles in HIV-1 infected Chinese population, consequently, the association of certain HLA alleles with susceptibility or resistance to HIV-1 infection would provide with clues in choosing proper preventive strategies against HIV-1 infection and developing effective HIV-1 vaccines in Chinese population, especially for those in southwest China.

摘要

背景

过去 3 年来,中国重庆的人类免疫缺陷病毒 1(HIV-1)疫情迅速上升,优势亚型为 CRF07_BC。由于人类白细胞抗原(HLA)多态性与不同种族背景的个体对 HIV-1 感染的易感性/抗性有很强的关联,最近对来自中国几个省份的 HIV 感染者中 HLA Ⅰ类和Ⅱ类等位基因的频率进行的调查也表明,在中国的其他省份也存在类似的相关性,但在中国西南部的重庆,这种信息是没有的。

方法

在这项基于人群的研究中,我们对来自中国重庆汉族的 549 名 HIV-1 感染者进行了聚合酶链反应分析与序列特异性寡核苷酸探针(PCR-SSOP)的中低分辨率 HLA 分型,另外还选择了来自中国重庆的 2475 名汉族健康受试者作为人群对照。我们比较了两组之间 HLA-A、B、DRB1 等位基因、单倍型和基因型的频率,并分析了它们与 HIV-1 易感性或抗性的关系。

结果

获得了来自中国重庆汉族 HIV-1 感染者的 HLA(A、B、DRB1)等位基因的遗传特征。一些 HLA-B 等位基因,如 B46(P=0.001,OR=1.38,95%CI=1.13-1.68)、B1501G(B62)(P=0.013,OR=1.42,95%CI=1.08-1.88)、B67(P=0.022,OR=2.76,95%CI=1.16-6.57)、B37(P=0.014,OR=1.93,95%CI=1.14-3.28)和 B52(P=0.038,OR=1.64,95%CI=1.03-2.61)与该人群中 HIV-1 感染的易感性有关。此外,单倍型分析显示,2 个位点的 A11-B46、A24-B54 和 A01-B37,以及 3 个位点的 A11-B46-DRB109、A02-B46-DRB108、A11-B4001G-DRB115、A02-B4001G-DRB104、A11-B46-DRB108 和 A02-B4001G-DRB112 在 HIV-1 感染者中显著过表达,而 A11-B1502G、A11-B1502G-DRB112 和 A33-B58-DRB1*13 则表达不足。然而,两组之间 HLA-A、B、DRB1 位点的低分辨率纯合性和 HLA-Bw4/Bw6 基因型没有显著差异。

结论

这些结果可能有助于 HIV-1 感染的中国人群 HLA 图谱数据库的建立,因此,某些 HLA 等位基因与 HIV-1 感染的易感性或抗性之间的关联将为选择针对 HIV-1 感染的适当预防策略和在中国人群中开发有效的 HIV-1 疫苗提供线索,特别是针对中国西南部的人群。

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