Research Article

HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma

  1. M. Tevfik Dorak1,†,
  2. Leland J. Yee2,‡,
  3. Jianming Tang1,
  4. Wenshuo Shao1,
  5. Elena S. Lobashevsky1,
  6. Lisa P. Jacobson2,
  7. Richard A. Kaslow1,*

Article first published online: 18 MAY 2005

DOI: 10.1002/jmv.20361

Issue

Journal of Medical Virology

Journal of Medical Virology

Volume 76, Issue 3, pages 302–310, July 2005

Additional Information

How to Cite

Dorak, M. T., Yee, L. J., Tang, J., Shao, W., Lobashevsky, E. S., Jacobson, L. P. and Kaslow, R. A. (2005), HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma. J. Med. Virol., 76: 302–310. doi: 10.1002/jmv.20361

Author Information

  1. 1

    Departments of Epidemiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama

  2. 2

    Department of Epidemiology, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland

  1. †

    School of Clinical Medical Sciences, University of Newcastle-upon-Tyne, Newcastle, UK.

  2. ‡

    Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA.

*Department of Epidemiology, School of Public Health, University of Alabama at Birmingham, 1665 University Boulevard, 220 Birmingham, AL 35294-0022.

Publication History

  1. Issue published online: 18 MAY 2005
  2. Article first published online: 18 MAY 2005
  3. Manuscript Accepted: 21 FEB 2004

Funded by

  • National Institute of Health (NIH). Grant Numbers: R01-CA75957, R01-CA106168
  • Center for AIDS Research (CFAR)
  • School of Public Health at UAB
  • National Institute of Allergy and Infectious Diseases
  • National Cancer Institute. Grant Numbers: UO1-AI-35042, 5-MO1-RR-00722 (GCRC), UO1-AI-35043, UO1-AI-37984, UO1-AI-35039, UO1-AI-35040, UO1-AI-37613, UO1-AI-35041

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Keywords:

  • AIDS-related opportunistic infections;
  • AIDS-related malignancies;
  • case-control studies;
  • polymorphism (genetics);
  • genetic markers;
  • HLA genes

Abstract

Polymorphisms of genes in the human leukocyte antigen (HLA) complex, particularly those encoding HLA-DR, have been suggested as markers of susceptibility to Kaposi's sarcoma (KS). We conducted a case-control study comparing 147 homosexual men who developed KS after infection by human immunodeficiency virus-1 (HIV-1) and human herpes virus 8 (HHV8) with 147 matched dually infected men without HIV-associated KS (HIV-KS) from the Multicenter AIDS Cohort Study. HLA-B, DRB1, DRB3, DRB4, DRB5, and DQB1 polymorphisms were examined by high-resolution DNA-based methods. Differences in distributions of genetic variants were tested by conditional logistic regression. Previously reported relationships with HLA-DRB1 alleles could not be confirmed. Instead, other associations were observed. In univariate analysis, KS was weakly associated with B*2702/5 (odds ratio (OR) = 0.40, 95% confidence interval (CI) = 0.18–0.91). Similar or stronger associations, positive or negative, were seen for haplotypes containing class II alleles: DRB1*1302-DQB1*0604 (OR = 3.67, 95% CI = 1.02–13.1), DRB4 (DR53) haplotype family members [OR = 0.52, 95% CI = 0.32–0.85], and DRB3 (DR52) haplotype family members (OR = 1.69, 95% CI = 1.07–2.67). The B*1402-DRB1*0102 haplotype, which invariably contains the V281L mutation in the 21-hydroxylase gene governing adrenal steroid biosynthesis, occurred in five cases and one control (OR = 5.0, 95% CI = 0.58–42.8). In a final multivariable analysis, only DRB1*1302-DQB1*0604 (OR = 6.43, 95% CI = 1.28–32.3, P = 0.02) remained significantly associated with KS. Associations of HLA-DRB families with HIV-KS could reflect underlying immune dysregulation. The HLA B*1402-DRB1*0102 haplotype associated with increased risk of KS might represent an antigen-presenting pathway unfavorable for immune response to HHV8. Alternatively, the relationship might hold a clue to the predilection of KS for men because that haplotype harbors the mutant form of the 21-hydroxylase gene. J. Med. Virol. 76:302–310, 2005. © 2005 Wiley-Liss, Inc.

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