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

Host immunogenetic factors such as HLA class I polymorphism are important to HIV-1infection risk and AIDS progression. Previous studies using high resolution HLA class Ⅰ profile data of Chinese populations appeared insufficient to provide information for HIV-1vaccine development and clinical trial design. Here we reported HLA class Ⅰ association with HIV-1susceptibility in a Chinese Han and a Chinese Uyghur cohort.Our cohort included327Han and161Uyghur ethnic individuals. Each cohort included HIV-1seropositive and HIV-1seronegative 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-1seropositive 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 identified58HLA-A,75HLA-B, and32HLA-Cw distinct alleles from our cohort and no novel alleles. The frequency of HLA-B*5201(OR=0.24,95%CI:0.10-0.57; p=0.001, q=0.026) and A*0301(OR=0.25,95%CI:0.09-0.64; p=0.002, q=0.030) was significantly higher in the Han HIV-1negative group. The frequency of HLA-B*5101(OR=0.18,95%CI:0.06-0.49; p=0.002, q=0.056) was significantly higher in the Uyghur HIV-1negative group. We observed statistically significant increases in expectation-maximization (EM) algorithm predicted haplotype frequencies of HLA-A*0201-B*5101in the Uyghur HIV-1negative group, and of Cw*0304-B*4001in the Han HIV-1negative group. The B62s supertype frequency was found to be significantly higher in the Han HIV-1negative group than in the Han HIV-1positive group.In conclusion, at the four-digit level, several HLA class Ⅰ alleles and haplotypes were associated with lower HIV-1susceptibility. Homogeneity of HLA class Ⅰ and Bw4/Bw6heterozygosity were not associated with HIV-1susceptibility in our cohort. These observations contribute to the Chinese HLA database and could prove useful in the development of HIV-1vaccine candidates.