Human leukocyte antigen-DQ alleles and haplotypes and their associations with resistance and susceptibility to HIV-1 infection
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Date
2008Author
Hardie, RA
Luo, M
Bruneau B
Knight, E
Nagelkerke, NJ
Kimani, J
Wachihi, C
Ngugi, Elizabeth N
Plummer, FA
Type
ArticleLanguage
enMetadata
Show full item recordAbstract
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 CD4þ and CD8þ T cell responses. As human
leukocyte antigen-DQ antigens present viral peptides to CD4þ 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 (P¼0.055, Odds Ratio¼12.77, 95%
Confidence Interval¼1.44–112), DQB1 0603 and DQB1 0609 (P¼0.037, Odds
Ratio¼3.25, 95%Confidence Interval¼1.12–9.47), andDQA1 010201–DQB1 0603
0603 (P¼0.044, Odds Ratio¼17.33, 95% Confidence Interval¼1.79–168). Conversely,
DQB1 0602 (P¼0.048,Odds Ratio¼0.68, 95%Confidence Interval¼0.44–1.05)
and DQA1 010201–DQB1 0602 (P¼0.039, Odds Ratio¼0.64, 95% Confidence
Interval¼0.41–1.03) 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 Ratio¼0.30-0.31, 95% Confidence Interval¼0.03–3.70), 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 ofDQalleles and haplotypes with resistance and susceptibility to HIV-1 emphasize the importance of human leukocyte antigen-DQ and CD4 in anti-HIV-1 immunity.
URI
http://www.ncbi.nlm.nih.gov/pubmed/18427198http://erepository.uonbi.ac.ke:8080/xmlui/handle/123456789/16175
Citation
AIDS. 2008 Apr 23;22(7):807-16.Publisher
Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada Department of Community Health, University of Nairobi, Department of Medical Microbiology, University of Manitoba, Winnipeg, Manitoba, Canada, Department of Community Medicine, United Arab Emirates University, Al-Ain, United Arab Emirates Medical Microbiology, Room 507, Basic Medical Sciences Building, 730 William Avenue,
Subject
Disease associationDisease resistance
DNA sequence analysis, HIV-1
Human leukocyte antigen-DQA1
Human leukocyte antigen-DQB1
Sex workers
Collections
- Faculty of Health Sciences (FHS) [10377]