title: Polymorphisms in the interleukin-4 receptor alpha chain gene influence susceptibility to HIV-1 infection and its progression to AIDS.
abstract: Interleukin (IL) 4 is a key T helper-2 cytokine that downregulates and upregulates CCR5 and CXCR4, respectively, the main coreceptors for HIV. Our objective is to investigate whether single-nucleotide polymorphisms (SNPs) in the IL-4 receptor alpha chain gene (IL4RA) affect HIV infection and its progression to AIDS. The I50V SNP in exon 5 and the haplotypes of six SNPs in exon 12 (E375A, C406R, S411L, S478P, Q551R, and V554I) were studied by polymerase chain reaction and sequencing in 30 HIV+ long-term nonprogressors (LTNP), 36 HIV+ typical progressors (TP), 55 highly exposed but uninfected individuals (EU), 25 EU-sexuals (EU-Sex; mostly women) and 30 EU-hemophiliacs (EU-Hem; hepatitis C virus+), and 97 healthy controls (HC), all Caucasians and lacking CCR5Delta32 homozygosity. V50 homozygosity was increased in LTNP (44%) compared with the other groups [p = 0.005; relative risk ratio = 3.4, 95% confidence interval (CI) = 1.12-10.6, p = 0.03]. The most common (C) exon 12 haplotype, ECSSQV, predominated in all groups, but uncommon (U) haplotypes were increased in HIV+ individuals (n = 64), especially in those (51 of 64) infected via parenteral exposure (35.3%) compared with HC (20.4%) and EU-Hem (18.4%) [p = 0.01; odds ratio (OR) = 2.14, 95% CI = 1.25-3.67, p = 0.01]. EU-Sex also had an increased frequency of U-haplotypes (34.8%) (OR = 2.10, 95% CI = 1.03-4.21, p = 0.01) as well as an increased frequency of CU + UU genotypes (60.9%) compared with HC (38.2%) and EU-Hem (26.6%) (p = 0.043). Distributions of genotypes fitted Hardy-Weinberg equilibrium. Data suggest that V50 homozygosity associates with slow progression and that exon 12 U-haplotypes might be associated with both susceptibility to infection via parenteral route and resistance to infection via sexual exposure. Further studies are required to confirm these findings.
authors.affiliation: Service of Infectious Diseases and AIDS Unit, Hospital Clínic de Barcelona, Villarroel, 170, 08036, Barcelona, Spain. asoriano@clinic.ub.es
authors.forename: Alex
authors.initials: A
authors.lastname: Soriano
authors.forename: Francisco
authors.initials: F
authors.lastname: Lozano
authors.forename: Harold
authors.initials: H
authors.lastname: Oliva
authors.forename: Felipe
authors.initials: F
authors.lastname: García
authors.forename: Meritxell
authors.initials: M
authors.lastname: Nomdedéu
authors.forename: Elisa
authors.initials: E
authors.lastname: De Lazzari
authors.forename: Carmen
authors.initials: C
authors.lastname: Rodríguez
authors.forename: Alicia
authors.initials: A
authors.lastname: Barrasa
authors.forename: José I
authors.initials: JI
authors.lastname: Lorenzo
authors.forename: Jorge
authors.initials: J
authors.lastname: Del Romero
authors.forename: Montserrat
authors.initials: M
authors.lastname: Plana
authors.forename: José M
authors.initials: JM
authors.lastname: Miró
authors.forename: José M
authors.initials: JM
authors.lastname: Gatell
authors.forename: Jordi
authors.initials: J
authors.lastname: Vives
authors.forename: Teresa
authors.initials: T
authors.lastname: Gallart
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000235:genetics; D005091:Exons; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D015658:HIV Infections / Q000235:genetics* / Q000473:pathology; D006239:Haplotypes; D006720:Homozygote; D006801:Humans; D053662:Interleukin-4 Receptor alpha Subunit; D008297:Male; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: C504000:IL4R protein, human; D053662:Interleukin-4 Receptor alpha Subunit; D021122:Protein Subunits; D011956:Receptors, Cell Surface