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- Title
Polymorphisms in the interleukin-4 receptor α chain gene influence susceptibility to HIV-1 infection and its progression to AIDS.
- Authors
Soriano, Alex; Lozano, Francisco; Oliva, Harold; García, Felipe; Nomdedéu, Meritxell; De Lazzari, Elisa; Rodríguez, Carmen; Barrasa, Alicia; Lorenzo, José I.; del Romero, Jorge; Plana, Montserrat; Miró, José M.; Gatell, José M.; Vives, Jordi; Gallart, Teresa
- 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 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.
- Subjects
INTERLEUKIN-4; GENETIC polymorphisms; HIV infections; AIDS; EXONS (Genetics); HEMOPHILIACS
- Publication
Immunogenetics, 2005, Vol 57, Issue 9, p644
- ISSN
0093-7711
- Publication type
Article
- DOI
10.1007/s00251-005-0041-x