Human leukocyte antigen-DQ alleles and haplotypes and their associations with resistance and susceptibility to HIV-1 infection

AIDS. 2008 Apr 23;22(7):807-16. doi: 10.1097/QAD.0b013e3282f51b71.

Abstract

Objectives: To determine the association of DQ antigens with resistance and susceptibility to HIV-1.

Design: Despite repeated exposure to HIV-1, a subset of women in the Pumwani Sex Worker cohort established in Nairobi, Kenya in 1985 have remained HIV-1 negative for at least 3 years and are classified as resistant. Differential susceptibility to HIV-1 infection is associated with HIV-1 specific CD4 and CD8 T cell responses. As human leukocyte antigen-DQ antigens present viral peptides to CD4 cells, we genotyped human leukocyte antigen -DQ alleles for 978 women enrolled in the cohort and performed cross-sectional and longitudinal analyses to identify associations of human leukocyte antigen -DQ with resistance/susceptibility to HIV-1.

Methods: DQA1 and DQB1 were genotyped using taxonomy-based sequence analysis. SPSS 13.0 was used to determine associations of DQ alleles/haplotypes with HIV-1 resistance, susceptibility, and seroconversion rates.

Results: Several DQB1 alleles and DQ haplotypes were associated with resistance to HIV-1 infection. These included DQB1*050301 (P = 0.055, Odds Ratio = 12.77, 95% Confidence Interval = 1.44-112), DQB1*0603 and DQB1*0609 (P = 0.037, Odds Ratio = 3.25, 95% Confidence Interval = 1.12-9.47), and DQA1*010201-DQB1*0603 (P = 0.044, Odds Ratio = 17.33, 95% Confidence Interval = 1.79-168). Conversely, DQB1*0602 (P = 0.048, Odds Ratio = 0.68, 95% Confidence Interval = 0.44-1.05) and DQA1*010201-DQB1*0602 (P = 0.039, Odds Ratio = 0.64, 95% Confidence Interval = 0.41-1.03) were overrepresented in the HIV-1 infected population. DQA1*0504-DQB1*0201, DQA1*010201-DQB1*0201, DQA1*0402-DQB1*0402 and DQA1*0402-DQB1*030101 genotypes were only found in HIV-1 positive subjects (Odds Ratio = 0.30-0.31, 95% Confidence Interval = 0.03-3.70), and these women seroconverted rapidly. The associations of these DQ alleles and haplotypes with resistance and susceptibility to HIV-1 were independent of the previously reported human leukocyte antigen-DRB*01, human leukocyte antigen A2/6802, and human leukocyte antigen-A*2301.

Conclusion: The associations of DQ alleles and haplotypes with resistance and susceptibility to HIV-1 emphasize the importance of human leukocyte antigen-DQ and CD4 in anti-HIV-1 immunity.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Confidence Intervals
  • Cross-Sectional Studies
  • Female
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • HIV Infections / genetics
  • HIV Infections / immunology*
  • HIV Seropositivity / genetics
  • HIV Seropositivity / immunology
  • HIV-1*
  • HLA-DQ Antigens / genetics*
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • Haplotypes
  • Humans
  • Longitudinal Studies
  • Membrane Glycoproteins / genetics
  • Odds Ratio
  • Sequence Analysis, DNA
  • Sex Work

Substances

  • HLA-DQ Antigens
  • HLA-DQ alpha-Chains
  • HLA-DQ beta-Chains
  • HLA-DQA1 antigen
  • HLA-DQB1 antigen
  • Membrane Glycoproteins