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 = 5.59 x 10(-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.