High Resolution Human Leukocyte Antigen Class I Allele Frequencies and HIV-1 Infection Associations in Chinese Han and Uyghur Cohorts

<div><h3>Background</h3><p>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.</p> <h3>Methodology/Principal Findings</h3><p>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.</p> <h3>Conclusions</h3><p>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.</p> </div

Common HLA class I inferred haplotype frequencies comparison in Uyghur HIV-1 positive and negative cohorts.

<p>Only haplotypes with estimated frequencies ≥0.02 are shown. The <i>q</i> values refer to comparisons between HIV-1 positive and HIV-1 negative groups.</p

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.

<p>Uyghur Cohort included our Uyghur HIV-1 positive and negative groups. Han Cohort included our Han HIV-1 positive and negative groups.</p

Common HLA class I allele frequencies comparison in Uyghur HIV-1 positive and negative cohorts.

<p>Only alleles with frequencies ≥0.01 are shown. The <i>q</i> values refer to comparisons between HIV-1 positive and HIV-1 negative groups.</p

Common HLA class I haplotypes in Chinese Uyghur and Han populations.

<p>Only haplotypes with estimated frequencies ≥0.02 are shown.</p

Common HLA class I allele frequencies comparison in Han HIV-1 positive and negative cohorts.

<p>Only alleles with frequencies ≥0.01 are shown. The <i>q</i> values refer to comparisons between HIV-1 positive and HIV-1 negative groups.</p

Common HLA class I alleles in Chinese Uyghur and Han populations.

<p>Uygur 2n = 322. Han 2n = 654. Alleles with frequencies lower than 0.01 in both Uyghur and Han cohorts are not shown.</p

Common HLA class I inferred haplotype frequencies comparison in Han HIV-1 positive and negative cohorts.

<p>Only haplotypes with estimated frequencies ≥0.02 are shown. The <i>q</i> values refer to comparisons between HIV-1 positive and HIV-1 negative groups.</p