Citation: Kun-xue HONG, Xiao-zhi LU, Guang-ming QIN, Jian-ping CHEN, Yu-hua RUAN, Hui XING, Jia-hong ZHU, Yi-ming SHAO. Relationship of HLA-A, -Cw Polymorphisms with HIV/AIDS in Chinese Yi Ethnic Group of Sichuan Province* .VIROLOGICA SINICA, 2007, 22(4) : 301-306.

Relationship of HLA-A, -Cw Polymorphisms with HIV/AIDS in Chinese Yi Ethnic Group of Sichuan Province*

  • Corresponding author: Yi-ming SHAO, yshao@bbn.cn
  • Received Date: 15 January 2007
    Accepted Date: 10 May 2007
    Available online: 01 August 2007

    Fund Project: 973 Program 2006 CB 504207the 10th Five-Years Key Technologies R & D Program 2004BA719A01

  • The relationship of HLA-A, -Cw alleles on HIV infection and AIDS disease progression in the Chinese Yi ethnic group of Sichuan province were investigated. The genetic polymorphisms of HLA-A, -Cw alleles of 102 unrelated healthy Chinese Yi ethnic individuals, 68 HIV-1 infected and 21 HIV positive long-time survivors were typed by PCR-SSP assay. Statistic signifiance was determined by the χ2 test with the SPSS software. No significant differences were observed between the HLA-A, -Cw alleles of the 68 HIV-1 infected and 102 non-infected Chinese Yi control individuals. Whereas the prevalence of A*3601,Cw*14(01-03)and Cw*0304 was significantly higher in 21 long time survivors compared with 102 healthy controls with P values of 0.016, 0.016 and 0.000 by χ2 or the Fisher exact test respectively. The result implies that A*3601,Cw*14(01-03) and Cw*0304 may be associated with slow AIDS disease progression in the Chinese Yi ethnic group, further studies on this association may yield insight on the pathogenesis of HIV-1 infection.

  • 加载中
    1. Bunce M, O'Neill C M, Barnardo M C, et al. Phototyping: comprehensive DNA typing for HLA-A, B, C, DRB1, DRB3, DRB4, DRB5, and DQB1 by 144 primer mixes utilizing sequence-specific primers (PCR-SSP). Tissue Antigens, 1995, 46: 355-367.
        doi: 10.1111/tan.1995.46.issue-5

    2. Carrington M, O'Brien S J. The influence of HLA genotype on AIDS. Annu Rev Med, 2003, 54: 535-551.
        doi: 10.1146/annurev.med.54.101601.152346

    3. Dorak M T, Tang J, Tang S, et al. Influence of human leukocyte antigen-B22 alleles on the course of human immunodeficiency virus type 1infection in 3 cohorts of white men. J Infect Dis, 2003, 188: 856-863.
        doi: 10.1086/jid.2003.188.issue-6

    4. Gore S M, Hutchinson S, Brettle R P, et al. Study requirements for investigating HLA-associated progression of HIV disease, and review. Quant J Med, 1999, 92: 609-617.

    5. Guo Z, Li X, He Y. 1996. Data Analysis of Medical Genetics and Genetic Epidemiology. Haerbing: Helongjiang Science and Technology Press, p1-50.

    6. MacDonald K S, Fowke K R, Kimani J, et al. Influence of HLA supertypes on susceptibility and resistance to human immunodeficiency virus typ1 infection. J Infect Dis, 2000, 181: 1581-1589.
        doi: 10.1086/jid.2000.181.issue-5

    7. Moore C B, John M, James I R, et al. Evidence of HIV-1 adaptation to HLA restricted. immune responses at a population level. Science, 2002, 296: 1439-1443.
        doi: 10.1126/science.1069660

    8. Qing M L, Li T S, Han Y, et al. Accelerating Effect of Human Leukocyte Antigen-Bw6 Homozygosity on Disease Progression in Chinese HIV-1-Infected Patients. J Acquir Immune Defic Syndr, 2006, 41: 137-139.
        doi: 10.1097/01.qai.0000195607.25262.92

    9. Sun Z R, Shang H, Zhang Y Z, et al. Studies of potential linkage between HLA classⅠalleles and HIV infection. Chin J Micro Immunol, 2003, 23 (3): 356-358.

    10. Welsh K I, Bunce M. Molecular typing for the MHC with PCR-SSP. Rev Immunogenet, 1999, 1: 157-176.

  • 加载中

Tables(2)

Article Metrics

Article views(3291) PDF downloads(19) Cited by()

Related
Proportional views

    Relationship of HLA-A, -Cw Polymorphisms with HIV/AIDS in Chinese Yi Ethnic Group of Sichuan Province*

      Corresponding author: Yi-ming SHAO, yshao@bbn.cn
    • 1. National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China
    • 2. Wuhan Institute of Biological Products, Wuhan 430060, China
    • 3. Sichuan Center for Disease Control and Prevention, Chendu 610000, China
    Fund Project:  973 Program 2006 CB 504207the 10th Five-Years Key Technologies R & D Program 2004BA719A01

    Abstract: The relationship of HLA-A, -Cw alleles on HIV infection and AIDS disease progression in the Chinese Yi ethnic group of Sichuan province were investigated. The genetic polymorphisms of HLA-A, -Cw alleles of 102 unrelated healthy Chinese Yi ethnic individuals, 68 HIV-1 infected and 21 HIV positive long-time survivors were typed by PCR-SSP assay. Statistic signifiance was determined by the χ2 test with the SPSS software. No significant differences were observed between the HLA-A, -Cw alleles of the 68 HIV-1 infected and 102 non-infected Chinese Yi control individuals. Whereas the prevalence of A*3601,Cw*14(01-03)and Cw*0304 was significantly higher in 21 long time survivors compared with 102 healthy controls with P values of 0.016, 0.016 and 0.000 by χ2 or the Fisher exact test respectively. The result implies that A*3601,Cw*14(01-03) and Cw*0304 may be associated with slow AIDS disease progression in the Chinese Yi ethnic group, further studies on this association may yield insight on the pathogenesis of HIV-1 infection.

    • Infection with human immunodeficiency virus type 1(HIV-1) and progression to acquired immunodeficiency syndrome (AIDS) are controlled by both viral factors and host genetic factors. It is increasingly clear that host genetic factors such as the human leukocyte antigen (HLA) alleles play important role in HIV-1 infection and disease progression. HLA is a region of genes on the short arm of chromosome 6, this region controls immune response functions and tissue rejection and influences susceptibility to many diseases. An increasing body of evidence is emerging regarding certain different HLA alleles involved in the susceptibility and/or resistance to HIV infection and disease progression in individuals of various ethnic backgrounds (2, 3, 6, 7). In the present study, we investigated the distribution of the HLA-A, Cw alleles in unrelated healthy Chinese Yi ethnic individuals in Sichuan province, where the prevalence of HIV infection is high, and then analyzed whether the presence of certain HLA-A, Cw alleles could be a factor affecting the susceptibility to HIV-1 infection and disease progression. The results may shed light on the pathogenesis of HIV-1 infection and will also have implications for the design and testing of candidate vaccines.

    • 102 healthy control and 68 HIV-1-positive blood samples from members of the Yi ethnic group were randomly collected from Lianshang Yi Autonomous Prefecture in Sichuan Province, which holds the single largest Yi community in China. The ethnicity of the subjects' parents was identified using a questionnaire. All of the subjects in this study did not report admixture outside their ethnic groups over at least one generation, and did not have any sib relationships over at least three generations. In addition, 21 HIV-1 infected long term survivors were also collected in this study, all these subjects remains disease-free and have a high number (≥ 500 cells/µL) of peripheral CD4+ T cells in the absence of antiretroviral therapy for 8 or more years of infection. All blood samples were collected after obtaining written informed consent. HIV serostatus was tested using Vironostika HIV Uni-Form II plus O kit (BioMerix, France) and confirmed by the GENELABS HIV BLOT 2.2 kit (Genelabs, USA).

    • Genomic DNA was isolated from 200 μL EDTA anticoagulated peripheral blood of healthy and HIV positive individuals using the QIAamp Blood DNA Mini Kit (Qiagen, USA) according to the manufacturer's instructions.

    • Low-resolution HLA-A, -Cw genotyping was carried out using the PCR-SSP assay. For the HLA-A, -Cw loci, twenty-four separate PCR reactions (including 23 allele PCR reactions and 1 negative PCR reaction) were performed for each sample for each locus, respectively. The HLA-A, -Cw loci sequence specific primers and internal positive control primers were designed on the basis of published sequence (1, 10) (Sunbiotech Company, Beijing, China). The internal control primers produce an amplicon of 796 bp from intron3 and 4 of HLA-DRB1. The final reaction volume (20μL) contained 50-100ng of genomic DNA, 10×PCR Buffer 2uL, 2.5mmol/L dNTPs 1.6μL, 25mmol/L MgCl21.6μL, 20μmol/L of each locus specific primer 1μL, 20μmol/L of each internal control primer, 1μL, 5U/ uL of Taq DNA Polymerase 0.2 uL (Takara-biotech, Japan), 1%~2%DMSO, and ddH2O was added to create a final volume of 20μL. The DNA amplifications were performed on a Gene Amp PCR system 9700 (Perkin-Elmer Corporation, USA). The cycling parameters were as follows: 1 minute denaturation at 96oC, followed by 5 cycles of 30 seconds at 96℃, 45 seconds at 68℃, 1 minute at 72℃; 21 cycles of 30 seconds at 96℃, 50 seconds at 63℃, 1 minute at 72℃; 4 cycles of 30 seconds at 96℃, 1 minute at 55℃, 2 minutes at 72℃, and 5 minutes at 72 ℃. The amplification products (10μL) were visualized on 1.5% agarose gels containing 0.5 μg/mL ethidium bromide after the addition of 2 μL 6×loading buffer. The gels were run at 150V for approximately 20 minutes in 1×TAE buffer and visualized using UV illumination.

    • The gene frequency (GF) for each allele was obtained by the method described in Data Analysis of Medical Genetics and Genetic Epidemiology (5). The Hardy-Weinberg equilibrium in healthy control subjects was calculated by the χ2 test with SPSS software. To compare the allele distribution between HIV-1 seropositive and seronegative groups, we applied the chi-square test and Fisher's exact test (two-tailed) using SAS version 8.0 (SAS Institute Inc., Cary, NC, USA). The strength of an association was indicated by an odds ratio (OR) with 95% confidence interval (CI), and P≤0.05 was accepted as indicating a significant difference. An OR of < 1 and 95% confidence interval (CI) of OR < 1 indicate protection, whereas an OR of > 1 and CI of OR > 1 was taken to indicate increased risk.

    • Table 1 presents the distribution of HLA-A、-Cw alleles among 102 healthy control subjects and 68 HIV infected individuals in the Chinese Yi ethnic group; 13 and 14 alleles (or allele-groups) were detected in HLA-A and HLA-Cw loci in 102 healthy Yi ethnic Chinese. Of them, A*02, A*11, A*24 and Cw*01, Cw*07, Cw*08 were the most common alleles with an allele frequency of 0.2206, 0.3186, 0.02353 and 0.3333, 0.2500, 0.1765 respectively. No HLA-A、-Cw alleles were observed with significant allelic frequency differences between HIV infected and uninfected individuals (P>0.05), suggesting no apparent associations between HLA-A、-Cw alleles and susceptibility to HIV-1 infection in the study population.

      Table 1.  Distribution of HLA-A、-Cw alleles among HIV infected and uninfected individuals in Chinese Yi group

    • Survivors and uninfected individuals Table 2 presents distribution of HLA-A、HLA-Cw alleles among 21 HIV positive long time survivors (LTS) and 102 control subjects in the Chinese Yi ethnic group; the prevalence of A*3601, Cw*14(01-03) and Cw*0304 was significantly higher in the LTS group compared with uninfected healthy controls with a P value of 0.016, 0.016 and 0.000 by χ2 or Fisher exact test respectively. This implicated A*3601, Cw*14(01-03) and Cw*0304 may be genetic factors associated with slow AIDS disease progression in the population.

      Table 2.  Distribution of HLA-A、-Cw alleles among HIV positive long time survivors and uninfected individuals in Chinese Yi group

    • The HLA were the first identified genetic factors which have associations with certain diseases. The HLA genes have been found to be associated with over 100 various diseases, of which many are autoimmune, some are infections, and some are neoplastic. As one of chronic infectious diseases caused by the lentivirus, AIDS is closely associated with HLA in its susceptibility and disease progression (2, 3, 6, 7). With the improvement of HLA genotyping techniques, investigation of association of HLA and AIDS has been further pursued.

      It is generally recognized that host genetic background should be considered when investigating HLA-disease association due to the dramatic differences of HLA alleles distributions in different ethnicities and regions. Certain HLA alleles are well evidenced to be influential on HIV-1 acquisition and disease progression. Using a case-controlled study, we observed that HLA-A*3601, -Cw*14(01-03) and -Cw*0304 alleles may have a beneficial effect on controlling HIV-1 disease progression though no HLA-A, -C alleles have been observed to affect HIV acquisition in this studied Chinese Yi ethnic group. It is suggested that conclusive HLA-associated HIV infection and disease progression analysis requires larger sample sizes, precise clinical classification, clear ethnical genetic background and a corresponding genetic model (4); To date, only a few HLA alleles including HLA-B*35、B*27 and B*57 has been confirmed to have consensus association with HIV/ AIDS due to the difficulties in fulfilling these requirements. In recent years, several studies reported that some of HLA alleles or supertypes are related to HIV-1 infection and disease progression in Chinese population. For example, -B35 associated with susceptibility to HIV-1 infection (9), -Bw6 homozygote associated with rapid disease progression, and -Bw4 homozygote associated with slow disease progression (8); these results imply that the Chinese population have both similar and unsimilar HLA association with HIV/ AIDS compared with data reported in other populations.

      HLA alleles determine the molecular targets of the cellular immune response. Genetic polymorphisms of the HLA gene result in concentrated amino-acid substitutions in the peptide-binding groove that produce variability in peptide epitope binding and presentation to T cells. At the population level, HLA diversity provides protection against epidemic infection, with the differing precise molecular targets of individuals' immune responses ensuring that immune-escape-adaptive mechanisms of an infectious organism are countered. For viruses with extreme heterogeneity such as HIV-1, certain HLA allele restricted CTL epitopes can produce more strong responses than other epitopes; these dominant CTL responses might be among those factors responsible for HIV acquisition and disease progression.

      To conclude, we demonstrated that HLA-A*3601, -Cw*14(01-03) and -Cw*0304 alleles occurred more frequently in HIV-1 infected long term survivors than in control subjects in the Chinese Yi ethnic individuals in Sichuan province, indicating these alleles may be associated with slow AIDS disease progression. Since China is known for her multinationalities, and each nationality may be characterized by a unique HLA allelic distribution and unique HIV epidemic features, analysis of HLA polymorphism in different populations and their association with HIV-1 infection and disease progression may provide useful information for understanding the pathogenesis of HIV-1 infection and for improving understanding of infectious disease patterns in different populations. Furthermore, the results of this study may be important in designing and testing effective vaccines in this high-risk population.

    Table (2) Reference (10) Relative (20)

    目录

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return