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. 2012;7(12):e50656.
doi: 10.1371/journal.pone.0050656. Epub 2012 Dec 12.

High resolution human leukocyte antigen class I allele frequencies and HIV-1 infection associations in Chinese Han and Uyghur cohorts

Yanhou Liu  1 , Zhongfang Zhao, Tianyi Li, Qi Liao, Nicholas Kushner, Neal Y Touzjian, Yiming Shao, Yongtao Sun, Amie J Strong, Yichen Lu
Affiliations

High resolution human leukocyte antigen class I allele frequencies and HIV-1 infection associations in Chinese Han and Uyghur cohorts

Yanhou Liu et al. PLoS One. 2012.

Abstract

Background: Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1 infection risk and AIDS progression. Previous studies using high-resolution HLA class I profile data of Chinese populations appeared insufficient to provide information for HIV-1 vaccine development and clinical trial design. Here we reported HLA class I association with HIV-1 susceptibility in a Chinese Han and a Chinese Uyghur cohort.

Methodology/principal findings: Our cohort included 327 Han and 161 Uyghur ethnic individuals. Each cohort included HIV-1 seropositive and HIV-1 seronegative subjects. Four-digit HLA class I typing was performed by sequencing-based typing and high-resolution PCR-sequence specific primer. We compared the HLA class I allele and inferred haplotype frequencies between HIV-1 seropositive and seronegative groups. A neighbor-joining tree between our cohorts and other populations was constructed based on allele frequencies of HLA-A and HLA-B loci. We identified 58 HLA-A, 75 HLA-B, and 32 HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201 and A*0301 was significantly higher in the Han HIV-1 negative group. The frequency of HLA-B*5101 was significantly higher in the Uyghur HIV-1 negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101 in the Uyghur HIV-1 negative group, and of Cw*0304-B*4001 in the Han HIV-1 negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1 negative group than in the Han HIV-1 positive group.

Conclusions: At the four-digit level, several HLA class I alleles and haplotypes were associated with lower HIV-1 susceptibility. Homogeneity of HLA class I and Bw4/Bw6 heterozygosity were not associated with HIV-1 susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1 vaccine candidates.

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Conflict of interest statement

Competing Interests: Please note that Neal Y. Touzjian, Amie J. Strong, Nick Kushner and Yichen Lu are employed by Vaccine Technologies Inc., which is a commercial company. VTI has a therapeutic HIV vaccine in the product development stages. There are no patents or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Common HLA class I allele frequencies comparison in Uyghur HIV-1 positive and negative cohorts.
Only alleles with frequencies ≥0.01 are shown. The q values refer to comparisons between HIV-1 positive and HIV-1 negative groups.
Figure 2
Figure 2. Common HLA class I allele frequencies comparison in Han HIV-1 positive and negative cohorts.
Only alleles with frequencies ≥0.01 are shown. The q values refer to comparisons between HIV-1 positive and HIV-1 negative groups.
Figure 3
Figure 3. Common HLA class I inferred haplotype frequencies comparison in Uyghur HIV-1 positive and negative cohorts.
Only haplotypes with estimated frequencies ≥0.02 are shown. The q values refer to comparisons between HIV-1 positive and HIV-1 negative groups.
Figure 4
Figure 4. Common HLA class I inferred haplotype frequencies comparison in Han HIV-1 positive and negative cohorts.
Only haplotypes with estimated frequencies ≥0.02 are shown. The q values refer to comparisons between HIV-1 positive and HIV-1 negative groups.
Figure 5
Figure 5. Phylogenetic tree constructed by the neighbor-joining method based on allele frequencies of HLA-A and HLA-B loci shows the relationships of our cohorts with other populations.
Uyghur Cohort included our Uyghur HIV-1 positive and negative groups. Han Cohort included our Han HIV-1 positive and negative groups.
See this image and copyright information in PMC

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