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

M. Tevfik Dorak, Leland J. Yee, Jianming Tang, Wenshuo Shao, Elena S. Lobashevsky, Lisa Paula Jacobson, Richard A. Kaslow

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)302-310
Number of pages9
JournalJournal of Medical Virology
Volume76
Issue number3
DOIs
StatePublished - Jul 2005

Fingerprint

Kaposi's Sarcoma
HLA Antigens
Haplotypes
HIV
Odds Ratio
Confidence Intervals
Genes
Steroid 21-Hydroxylase
Alleles
Dichlororibofuranosylbenzimidazole
Viruses
HIV-1
Case-Control Studies
Acquired Immunodeficiency Syndrome
Cohort Studies
Logistic Models
Steroids
Antigens
Mutation
DNA

Keywords

  • AIDS-related malignancies
  • AIDS-related opportunistic infections
  • Case-control studies
  • Genetic markers
  • HLA genes
  • Polymorphism (genetics)

ASJC Scopus subject areas

  • Virology

Cite this

HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma. / Dorak, M. Tevfik; Yee, Leland J.; Tang, Jianming; Shao, Wenshuo; Lobashevsky, Elena S.; Jacobson, Lisa Paula; Kaslow, Richard A.

In: Journal of Medical Virology, Vol. 76, No. 3, 07.2005, p. 302-310.

Research output: Contribution to journalArticle

Dorak, M. Tevfik ; Yee, Leland J. ; Tang, Jianming ; Shao, Wenshuo ; Lobashevsky, Elena S. ; Jacobson, Lisa Paula ; Kaslow, Richard A. / HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma. In: Journal of Medical Virology. 2005 ; Vol. 76, No. 3. pp. 302-310.
@article{297fb3f13bb447ceb11546cba267fb4c,
title = "HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma",
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.",
keywords = "AIDS-related malignancies, AIDS-related opportunistic infections, Case-control studies, Genetic markers, HLA genes, Polymorphism (genetics)",
author = "Dorak, {M. Tevfik} and Yee, {Leland J.} and Jianming Tang and Wenshuo Shao and Lobashevsky, {Elena S.} and Jacobson, {Lisa Paula} and Kaslow, {Richard A.}",
year = "2005",
month = "7",
doi = "10.1002/jmv.20361",
language = "English (US)",
volume = "76",
pages = "302--310",
journal = "Journal of Medical Virology",
issn = "0146-6615",
publisher = "Wiley-Liss Inc.",
number = "3",

}

TY - JOUR

T1 - HLA-B, -DRB1/3/4/5, and -DQB1 gene polymorphisms in human immunodeficiency virus-related Kaposi's sarcoma

AU - Dorak, M. Tevfik

AU - Yee, Leland J.

AU - Tang, Jianming

AU - Shao, Wenshuo

AU - Lobashevsky, Elena S.

AU - Jacobson, Lisa Paula

AU - Kaslow, Richard A.

PY - 2005/7

Y1 - 2005/7

N2 - 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.

AB - 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.

KW - AIDS-related malignancies

KW - AIDS-related opportunistic infections

KW - Case-control studies

KW - Genetic markers

KW - HLA genes

KW - Polymorphism (genetics)

UR - http://www.scopus.com/inward/record.url?scp=20044369926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=20044369926&partnerID=8YFLogxK

U2 - 10.1002/jmv.20361

DO - 10.1002/jmv.20361

M3 - Article

C2 - 15902698

AN - SCOPUS:20044369926

VL - 76

SP - 302

EP - 310

JO - Journal of Medical Virology

JF - Journal of Medical Virology

SN - 0146-6615

IS - 3

ER -