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.
authors.affiliation: Department of Epidemiology and Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294-0022, USA.
authors.forename: M Tevfik
authors.initials: MT
authors.lastname: Dorak
authors.forename: Leland J
authors.initials: LJ
authors.lastname: Yee
authors.forename: Jianming
authors.initials: J
authors.lastname: Tang
authors.forename: Wenshuo
authors.initials: W
authors.lastname: Shao
authors.forename: Elena S
authors.initials: ES
authors.lastname: Lobashevsky
authors.forename: Lisa P
authors.initials: LP
authors.lastname: Jacobson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Kaslow
mesh_terms: D016022:Case-Control Studies; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000150:complications*; D015235:HLA-B Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D019288:Herpesvirus 8, Human / Q000302:isolation & purification; D018451:Homosexuality, Male; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D012514:Sarcoma, Kaposi / Q000209:etiology / Q000235:genetics*; D013255:Steroid 21-Hydroxylase / Q000235:genetics
chemical_list: D005819:Genetic Markers; D015235:HLA-B Antigens; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C057615:HLA-DQbeta antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D013255:Steroid 21-Hydroxylase