Exhaustive genotyping of the interleukin-1 family genes and associations with AIDS progression in a French cohort.
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.
Do
Herve
H
Centre National de Genotypage, Evry, Conservatoire National des Arts et Metiers, Paris, France.
Vasilescu
Alexandre
A
Carpentier
Wassila
W
Meyer
Laurence
L
Diop
Gora
G
Hirtzig
Thomas
T
Coulonges
Cedric
C
Labib
Taoufik
T
Spadoni
Jean-Louis
JL
Therwath
Amu
A
Lathrop
Mark
M
Matsuda
Fumihiko
F
Zagury
Jean-Francois
JF
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
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