title: 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 IL1 alpha , IL1 beta , IL1Ra, and IL1R1 genes in 245 slow progressor (SP) and 82 rapid progressor (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-1Ra 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.
authors.affiliation: Centre National de Genotypage, Evry, Conservatoire National des Arts et Metiers, Paris, France.
authors.forename: Herve
authors.initials: H
authors.lastname: Do
authors.forename: Alexandre
authors.initials: A
authors.lastname: Vasilescu
authors.forename: Wassila
authors.initials: W
authors.lastname: Carpentier
authors.forename: Laurence
authors.initials: L
authors.lastname: Meyer
authors.forename: Gora
authors.initials: G
authors.lastname: Diop
authors.forename: Thomas
authors.initials: T
authors.lastname: Hirtzig
authors.forename: Cedric
authors.initials: C
authors.lastname: Coulonges
authors.forename: Taoufik
authors.initials: T
authors.lastname: Labib
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Spadoni
authors.forename: Amu
authors.initials: A
authors.lastname: Therwath
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Matsuda
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Zagury
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D005602:France; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein / Q000235:genetics*; D053582:Interleukin-1alpha / Q000235:genetics*; D053583:Interleukin-1beta / Q000235:genetics*; D011110:Polymorphism, Genetic; D053573:Receptors, Interleukin-1 Type I / Q000235:genetics*; D013223:Statistics as Topic; D044465:White People
chemical_list: C508590:IL1R1 protein, human; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D053582:Interleukin-1alpha; D053583:Interleukin-1beta; D053573:Receptors, Interleukin-1 Type I