Journal Article

Polymorphisms in the interleukin-4 receptor α chain gene influence susceptibility to HIV-1 infection and its progression to AIDS

Miró, José M, Oliva, Harold, Lorenzo, José I, Lozano, Francisco, De Lazzari, Elisa, del Romero, Jorge, Barrasa, Alicia, Nomdedéu, Meritxell, Soriano, Alex, García, Felipe, Plana, Montserrat, Gatell, José M, Rodríguez, Carmen, Vives, Jordi, Gallart, Teresa

2005

Overview

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 α 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 CCR5Δ32 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.

• Publisher: Berlin/Heidelberg : Springer-Verlag
• Subject: Acquired Immunodeficiency Syndrome - genetics / Exons / Exposed but uninfected / Female / Gene Frequency / Genetic Predisposition to Disease / Genotype / Haplotypes / HIV infection / HIV Infections - genetics / HIV Infections - pathology / Homozygote / Human immunodeficiency virus 1 / Humans / Interleukin-4 Receptor alpha Subunit / Interleukin-4 receptor α chain / Long-term nonprogressors / Male / Polymorphism, Single Nucleotide / Protein Subunits - genetics / Receptors, Cell Surface - genetics / Single-nucleotide polymorphisms