Articles producció científica> Medicina i Cirurgia

Effect of TNF-a genetic variants and CCR5 Delta 32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards

  • Dades identificatives

    Identificador: imarina:625163
    Autors:
    Veloso, SOlona, MGarcía, FDomingo, PAlonso-Villaverde, CBroch, MPeraire, JViladés, CPlana, MPedrol, ELópez-Dupla, MAguilar, CGutiérrez, MLeon, ATasias, MGatell, JMRichart, CVidal, F
    Resum:
    Tumor necrosis factor alpha (TNF-alpha) is thought to be involved in the various immunogenetic events that influence HIV-1 infection.We aimed to determine whether carriage of the TNF-alpha-238G>A, -308G>A and -863 C>A gene promoter single nucleotide polymorphisms (SNP) and the CCR5 Delta 32 variant allele influence the risk of HIV-1 infection and disease progression in Caucasian Spaniards. The study group consisted of 423 individuals. Of these, 239 were uninfected (36 heavily exposed but uninfected [EU] and 203 healthy controls [HC]) and 184 were HIV-1-infected (109 typical progressors [TP] and 75 long-term nonprogressors [LTNP] of over 16 years' duration). TNF-alpha SNP and the CCR5 Delta 32 allele were assessed using PCR-RFLP and automatic sequencing analysis methods on white blood cell DNA. Genotype and allele frequencies were compared using the chi 2 test and the Fisher exact test. Haplotypes were compared by logistic regression analysis.The distribution of TNF-alpha-238G>A, -308G>A and -863 C>A genetic variants was non-significantly different in HIV-1-infected patients compared with uninfected individuals: -238G>A, p = 0.7 and p = 0.3; -308G>A, p = 0.05 and p = 0.07; -863 C>A, p = 0.7 and p = 0.4, for genotype and allele comparisons, respectively. Haplotype analyses, however, indicated that carriers of the haplotype H3 were significantly more common among uninfected subjects (p = 0.04). Among the infected patients, the distribution of the three TNF-alpha genetic variants assessed was non-significantly different between TP and LTNP: -238G>A, p = 0.35 and p = 0.7; -308G>A, p = 0.7 and p = 0.6: -863 C>A, p = 0.2 and p = 0.2, for genotype and allele comparisons, respectively. Haplotype analyses also indicated non-significant associations. Subanalyses in the LTNP subset
  • Altres:

    Autor segons l'article: Veloso, S; Olona, M; García, F; Domingo, P; Alonso-Villaverde, C; Broch, M; Peraire, J; Viladés, C; Plana, M; Pedrol, E; López-Dupla, M; Aguilar, C; Gutiérrez, M; Leon, A; Tasias, M; Gatell, JM; Richart, C; Vidal, F
    Departament: Medicina i Cirurgia
    Autor/s de la URV: Aguilar Crespillo, Carmen Isabel / López Dupla, Jesús Miguel / Richart Jurado, Cristobal Manuel / SIRVENT CALVERA, JUAN JOSÉ / Veloso Esteban, Sergio / Vidal Marsal, Francisco
    Paraules clau: Type-1 Tumor-necrosis-factor Susceptibility Polymorphisms Linkage disequilibrium Human-immunodeficiency-virus Cohort Aids
    Resum: Tumor necrosis factor alpha (TNF-alpha) is thought to be involved in the various immunogenetic events that influence HIV-1 infection.We aimed to determine whether carriage of the TNF-alpha-238G>A, -308G>A and -863 C>A gene promoter single nucleotide polymorphisms (SNP) and the CCR5 Delta 32 variant allele influence the risk of HIV-1 infection and disease progression in Caucasian Spaniards. The study group consisted of 423 individuals. Of these, 239 were uninfected (36 heavily exposed but uninfected [EU] and 203 healthy controls [HC]) and 184 were HIV-1-infected (109 typical progressors [TP] and 75 long-term nonprogressors [LTNP] of over 16 years' duration). TNF-alpha SNP and the CCR5 Delta 32 allele were assessed using PCR-RFLP and automatic sequencing analysis methods on white blood cell DNA. Genotype and allele frequencies were compared using the chi 2 test and the Fisher exact test. Haplotypes were compared by logistic regression analysis.The distribution of TNF-alpha-238G>A, -308G>A and -863 C>A genetic variants was non-significantly different in HIV-1-infected patients compared with uninfected individuals: -238G>A, p = 0.7 and p = 0.3; -308G>A, p = 0.05 and p = 0.07; -863 C>A, p = 0.7 and p = 0.4, for genotype and allele comparisons, respectively. Haplotype analyses, however, indicated that carriers of the haplotype H3 were significantly more common among uninfected subjects (p = 0.04). Among the infected patients, the distribution of the three TNF-alpha genetic variants assessed was non-significantly different between TP and LTNP: -238G>A, p = 0.35 and p = 0.7; -308G>A, p = 0.7 and p = 0.6: -863 C>A, p = 0.2 and p = 0.2, for genotype and allele comparisons, respectively. Haplotype analyses also indicated non-significant associations. Subanalyses in the LTNP subset indicated that the TNF-alpha-238A variant allele was significantly overrepresented in patients who spontaneously controlled plasma viremia compared with those who had a detectable plasma viral load (genotype comparisons, p = 0.02; allele comparisons, p = 0.03). The CCR5 Delta 32 distribution was non-significantly different in HIV-1-infected patients with respect to the uninfected population (p = 0.15 and p = 0.2 for genotype and allele comparisons, respectively) and in LTNP vs TP (p = 0.4 and p = 0.5 for genotype and allele comparisons, respectively).In our cohort of Caucasian Spaniards, TNF-alpha genetic variants could be involved in the vulnerability to HIV-1 infection. TNF-alpha genetic variants were unrelated to disease progression in infected subjects. The -238G>A SNP may modulate the control of viremia in LTNP. Carriage of the CCR5 Delta 32 variant allele had no effect on the risk of infection and disease progression.
    Àrees temàtiques: Saúde coletiva Química Odontología Nutrição Medicina iii Medicina ii Medicina i Matemática / probabilidade e estatística Interdisciplinar Genetics (clinical) Genetics & heredity Genetics Farmacia Engenharias iv Engenharias iii Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología Biodiversidade
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 14712350
    Adreça de correu electrònic de l'autor: cristobalmanuel.richart@urv.cat sergio.veloso@urv.cat jesusmiguel.lopez@urv.cat francesc.vidal@urv.cat carmenisabel.aguilar@urv.cat carmenisabel.aguilar@urv.cat
    Identificador de l'autor: 0000-0003-0852-6739 0000-0002-9141-2523 0000-0002-6692-6186 0000-0002-4440-562X 0000-0002-4440-562X
    Data d'alta del registre: 2024-06-28
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://bmcmedgenet.biomedcentral.com/articles/10.1186/1471-2350-11-63
    Referència a l'article segons font original: Bmc Medical Genetics. 11 (1): 63-
    Referència de l'ítem segons les normes APA: Veloso, S; Olona, M; García, F; Domingo, P; Alonso-Villaverde, C; Broch, M; Peraire, J; Viladés, C; Plana, M; Pedrol, E; López-Dupla, M; Aguilar, C; G (2010). Effect of TNF-a genetic variants and CCR5 Delta 32 on the vulnerability to HIV-1 infection and disease progression in Caucasian Spaniards. Bmc Medical Genetics, 11(1), 63-. DOI: 10.1186/1471-2350-11-63
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    DOI de l'article: 10.1186/1471-2350-11-63
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2010
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Genetics,Genetics & Heredity,Genetics (Clinical)
    Type-1
    Tumor-necrosis-factor
    Susceptibility
    Polymorphisms
    Linkage disequilibrium
    Human-immunodeficiency-virus
    Cohort
    Aids
    Saúde coletiva
    Química
    Odontología
    Nutrição
    Medicina iii
    Medicina ii
    Medicina i
    Matemática / probabilidade e estatística
    Interdisciplinar
    Genetics (clinical)
    Genetics & heredity
    Genetics
    Farmacia
    Engenharias iv
    Engenharias iii
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Biotecnología
    Biodiversidade
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