title: Differential prevalence of the HLA-C -- 35 CC genotype among viremic long term non-progressor and elite controller HIV+ individuals.
abstract: Susceptibility to HIV infection and disease progression are complex traits modulated by environmental and genetic factors, affecting innate and adaptive immune responses, among other cellular processes. A single nucleotide polymorphism (SNP) 35 kb upstream of the HLA-C gene locus (-35C/T) was previously shown to correlate with increased HLA-C expression and improved control of HIV-1. Here, we genotyped the -35C/T SNP in 639 subjects (180 uninfected patients, 304 HIV progressors and 155 LTNP) and confirmed the association of the -35C/T variant with the LTNP phenotype. The genotype frequencies in the general population subjects did not differ significantly from those seen in HIV progressors (p-value=0.472). However, a significant higher frequency of the protective CC genotype was identified when LTNP were compared either with HIV progressors alone (p-value<0.0001) or progressors and uninfected subjects together (p-value<0.0001). When considering aviremic LTNP alone (elite controllers; viral load below 50 copies/ml), the -35 CC genotype was not overrepresented compared to HIV progressors. Conversely, a significant association was found with the viremic LTNP groups (viral loads below 10,000 copies/ml). These results suggest that other factors alone or in combination with the -35 CC genotype may play an important role in differentiating the elite controller status from LTNP. Combination of different genetic variants may have additive or epistatic effects determining the HIV course of infection.
authors.affiliation: IrsiCaixa-HIVACAT, Hospital Universitari Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
authors.forename: Ester
authors.initials: E
authors.lastname: Ballana
authors.forename: Alba
authors.initials: A
authors.lastname: Ruiz-de Andres
authors.forename: Beatriz
authors.initials: B
authors.lastname: Mothe
authors.forename: Eva
authors.initials: E
authors.lastname: Ramirez de Arellano
authors.forename: Francisco
authors.initials: F
authors.lastname: Aguilar
authors.forename: Roger
authors.initials: R
authors.lastname: Badia
authors.forename: Eulalia
authors.initials: E
authors.lastname: Grau
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
authors.forename: Margarita
authors.initials: M
authors.lastname: del Val
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
authors.forename: José A
authors.initials: JA
authors.lastname: Esté
mesh_terms: D000483:Alleles; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology* / Q000821:virology; D020276:HIV Long-Term Survivors; D015236:HLA-C Antigens / Q000235:genetics*; D006801:Humans; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014766:Viremia / Q000235:genetics* / Q000276:immunology* / Q000821:virology
chemical_list: D015236:HLA-C Antigens