Associations of the IL2Ralpha, IL4Ralpha, IL10Ralpha, and IFN (gamma) R1 cytokine receptor genes with AIDS progression in a French AIDS cohort.
We have performed an extensive analysis of Th1/Th2 cytokine receptors IL2Ralpha, IL4Ralpha, IL10Ralpha, and IFNgammaR1 gene polymorphisms to evaluate their impact on AIDS progression. The coding regions and promoters of these genes were sequenced in the genetics of resistance to immunodeficiency virus cohort, composed of 327 HIV-1-positive patients with extreme progression phenotypes, slow and rapid progressors, and of 446 healthy control subjects, all of them of Caucasian descent. Overall, 104 single nucleotide polymorphisms and four insertions/deletions with a minor allelic frequency higher than 1% were identified, 21 of them being newly characterized. We observed weak associations for 13 polymorphisms of IL2Ralpha, IL4Ralpha, IL10Ralpha, and IFNgammaR1, and 11 haplotypes of IL2Ralpha, IL4Ralpha, and IFNgammaR1. However, we could not relate these positive signals to any relevant biological information on the gene function. To affirm these putative associations in AIDS, further confirmation on other AIDS cohorts will be needed. This complete catalog of polymorphisms in IL2Ralpha, IL4Ralpha, IL10Ralpha, and IFNgammaR1 cytokine receptor genes should also be useful for investigating associations in other immune-related diseases.
Do
Hervé
H
Equipe génomique, bioinformatique et pathologies du système immunitaire, INSERM U736, 15 rue de l'Ecole de Médecine, 75006, Paris, France.
Vasilescu
Alexandre
A
Diop
Gora
G
Hirtzig
Thomas
T
Coulonges
Cédric
C
Labib
Taoufik
T
Heath
Simon C
SC
Spadoni
Jean-Louis
JL
Therwath
Amu
A
Lathrop
Mark
M
Matsuda
Fumihiko
F
Zagury
Jean-François
JF
D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology; D015331:Cohort Studies; D018450:Disease Progression; D005602:France; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit; D053662:Interleukin-4 Receptor alpha Subunit; D020641:Polymorphism, Single Nucleotide; D017471:Receptors, Interferon / Q000235:genetics*; D018123:Receptors, Interleukin / Q000235:genetics*; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2 / Q000235:genetics; D019948:Receptors, Interleukin-4 / Q000235:genetics; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology; D000096743:Interferon gamma Receptor
D053645:Interleukin-2 Receptor alpha Subunit; D053662:Interleukin-4 Receptor alpha Subunit; D017471:Receptors, Interferon; D018123:Receptors, Interleukin; D053701:Receptors, Interleukin-10; D015375:Receptors, Interleukin-2; D019948:Receptors, Interleukin-4; D000096743:Interferon gamma Receptor; C508017:IL2RA protein, human; C504000:IL4R protein, human