Exhaustive genotyping of the interleukin-1 family genes and associations with AIDS progression in a French cohort

Abstract

Interleukin (IL)-1 family members are key players in inflammatory processes but have been the subject of few studies of acquired immunodeficiency syndrome (AIDS). To better evaluate the impact of the IL-1 family on AIDS development, we genotyped the IL1α, IL1β, IL1Ra, and IL1R1 genes in 245 slow progresser (SP) and 82 rapid progresser (RP) human immunodeficiency virus type 1-seropositive patients as well as in 446 control subjects, all of whom were of white ethnicity. One hundred sixteen frequent polymorphisms were identified, of which 23 were newly characterized by our study. Many putative associations were found between single-nucleotide polymorphism (SNP) or haplotype alleles and the extreme profiles of progression. Most of them corresponded to weak associations (.01 < P < .05); however, the SNP IL1Ra_2134 exhibited a consistent association, found at the level of the SNP, haplotypes, and haploblocks, when the SP and control populations were compared (P = .0002). The IL-1-dependent inflammatory response is, thus, likely to play a role in AIDS progression via the regulation of IL-IRa expression. This association will need to be confirmed in other AIDS cohorts, and experiments will also have to be performed to unravel the biological mechanisms at work. The data presented here will be useful for future genomic studies of the IL-1 family members in other infectious and chronic inflammatory diseases. © 2006 by the Infectious Diseases Society of America. All rights reserved.