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The Complexity of HLA Class II(DRB1, DQB1, DM)Associations With DisseminatedMycobacterium AviumComplex Infection Among HIV-1-Seropositive Whites

Naik Eknath; LeBlanc, Susan; Tang, Jianming; Jacobson, Lisa P.; Kaslow, Richard A.
JAIDS Journal of Acquired Immune Deficiency Syndromes: June 1st, 2003
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Summary:Earlier associations of polymorphism in classic HLA class II (DRB1 and DQB1) genes have been extended to include the accessory genes DMA and DMB as determinants of disseminated Mycobacterium avium complex (DMAC) infection among HIV-1-seropositive whites. From the Multicenter AIDS Cohort study, 176 DMAC cases were matched with 176 controls in a nested case-control study. PCR-based HLA genotyping techniques were used to resolve variants of DRB1 and DQB1 to their four-digit or five-digit alleles, and single-strand conformation polymorphism was used to resolve sequences in exon 3 at each DM locus. The DMA*0102 allele occurred less frequently among DMAC cases than among controls (OR = 0.46, p = .02). Combinations of DRB1 alleles with or without specific DMA and DMB variants showed significant differences in distributions between the cases and controls, but both of the previously associated class II alleles (DRB1*1501 and DRB1*0701) showed stronger positive associations with DMAC in the absence than in the presence of DMA*0102. Apparent joint effects of DRBI and DM allelic combinations on occurrence and timing of DMAC suggest that class II disease relationships may be better predicted by biologically plausible interactive combinations than by polymorphisms in individual genes.

Address correspondence and reprint requests to Richard A. Kaslow, Program in Epidemiology of Infection and Immunity, School of Public Health, 220A Ryals Building, 1665 University Boulevard, University of Alabama at Birmingham, Birmingham, AL 39294-0022. E-mail: rkaslow@uab.edu

Manuscript received September 13, 2002; accepted April 3, 2003.

© 2003 Lippincott Williams & Wilkins, Inc.