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

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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