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 P.
AU - Kaslow, Richard A.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
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
SN - 0146-6615
VL - 76
SP - 302
EP - 310
JO - Journal of Medical Virology
JF - Journal of Medical Virology
IS - 3
ER -