Title:Identification of IL7RA Risk Alleles for Rapid Progression During HIV-1 Infection: A Comprehensive Study in the GRIV Cohort
Volume: 10
Issue: 2
Author(s): Sophie Limou, Giovanna Melica, Cedric Coulonges, Jean-Daniel Lelievre, Herve Do, Steven McGinn, Ivo G. Gut, Yves Levy and Jean-Francois Zagury
Affiliation:
Keywords:
Genetic association study, haplotype, HIV, IL7RA, rapid progression, SNP, T cell homeostasis
Abstract: Interleukin 7 (IL7) is a critical factor for lymphocyte homeostasis. A dysfunction of the IL7/IL7R pathway has
previously been described in HIV-1 infection, and promising results were observed in recent analyses of IL7 for
therapeutic use in HIV infected individuals. However, further investigations are still warranted to understand the possible
roles of this cytokine. Here, we explored whether the IL7 and IL7RA genetic polymorphisms were associated with the
progression of HIV infection. We extensively genotyped the IL7 and IL7RA genes in the GRIV (Genomics of Resistance
to Immunodeficiency Virus) cohort, composed of patients with extreme progression profiles - long-term non (LTNP) and
rapid (RP) progressors -, and in a healthy control group (CTR). Statistical case-control analyses were performed using the
Fisher’s exact test, comparing either LTNP vs CTR or RP vs CTR. Three IL7RA SNPs (single nucleotide polymorphisms -
rs7701176, rs987106 and rs10491434), but no IL7 SNPs, were significantly associated with rapid disease progression
(P<0.01). In a multi-marker analysis focusing on functional variants, a strong association between an IL7RA haplotype
and rapid progression was observed (P=5.59x10-3). In summary, our comprehensive genetic study revealed three SNPs
and a risk of haplotype associated with rapid progression to AIDS in the IL7RA gene. Interestingly, the haplotype is
composed of SNPs previously identified in other inflammatory diseases (e.g., multiple sclerosis) by GWAS and by
functional studies. Our results contribute to the growing understanding of the role of IL7/IL7R in HIV disease
progression, and more widely, in CD4+ T cell homeostasis.
