RESUMO
RESUMEN Objetivo: Evaluar el impacto de los polimorfismos de los genes TNFA e IL10 y su asociación con el fenotipo clínico de la artritis psoriásica (APs). Materiales y métodos: Se incluyó a 104 individuos venezolanos, no relacionados, agrupados en 52 pacientes con APs, que reunieron los criterios CASPAR, y 52 individuos sanos, sin antecedentes familiares de psoriasis. Los polimorfismos de los genes TNFA e IL10 se determinaron por PCR-SSP. Resultados: El genotipo GA y alelo A del polimorfismo TNFA-238G/A parecen conferir protección contra el desarrollo de APs (OR: 0,31, IC del 95%: 0,92 -1,05, p: 0,02). El genotipo GA del polimorfismo TNFA-308G/A está asociado con una edad de inicio de APs tardía (GA = 60 ± 13,17 arios vs. GG = 43,55 ± 14,29 años; p = 0,002) y el genotipo GG del polimorfismo IL10-1082A/G con un intervalo mayor entre el inicio de la psoriasis y el desarrollo de la APs (GG = 27,4 ± 24,11 años, GA = 5,47 ± 7,23 años, AA = 7,86 ± 8,51 años, p = 0,001). Los genotipos CC de IL10-819 C/T e IL10-592 C/A confieren riesgo de daño a las articulaciones interfalángicas distales (OR: 4,79, p=0,026). Conclusiones: El polimorfismo TNFA-238G/A desempeña un papel importante en el desarrollo de la APs en mestizos venezolanos. Asimismo, los polimorfismos TNFA-308G/A, IL10-1082A/G, -819C/T y -592C/A pueden modificar la expresión clínica de la APs.
ABSTRACT Objective: To evaluate the impact of polymorphisms of TNF-alpha (TNFA) and IL10 genes and their association with clinical phenotypes of psoriatic arthritis (PsA). Materials and methods: The study included 104 unrelated Venezuelan individuals, grouped into 52 patients with PsA, who fulfilled the CASPAR criteria, and 52 healthy individuals with no family history of psoriasis. The polymorphisms of the TNFA and IL10 genes were determined by Single Specific Primer-Polymerase Chain Reaction (SSP-PCR). Results: The GA genotype and A allele of the TNFA-238G/A polymorphism appears to confer protection against the development of PsA (OR: 0.31, 95% CI: 0.92 -1.05, P=.02). The GA genotype of the TNFA-308G/A polymorphism is associated with a late onset age of PsA (GA = 60± 13.17 years vs. GG = 43.55 ± 14.29 years, P=.002), and the GG genotype of the IL10 -1082A/G polymorphism with a longer time interval between the onset of psoriasis and the development of PsA (GG = 27.4±24.11 years, GA = 5.47±7.23 years, AA=7.86±8.51 years, P=.001). The CC genotypes of IL10-819 C/T and IL10-592 C/A confers risk of damage to distal interphalangeal joints (OR: 4.79, P=.026) Conclusions: The TNFA-238G/A polymorphism plays an important role in the development of PsA in mixed-race Venezuelans. Likewise, TNFA-308 G/A, IL10 -1082 A/G, -819C/T, -592C/A polymorphisms may modify the clinical expression of PsA.
Assuntos
Artrite Psoriásica , Genes , Fenótipo , Associação , Sinais e Sintomas , GenótipoRESUMO
Cell-mediated immunity requires costimulatory activity to initiate or inhibit antigen-specific T-cell responses. CTLA-4 is an inhibitory receptor expressed by activated and regulatory T cells. The single nucleotide polymorphism (SNP) +49 A/G of the CTLA-4 gene alters intracellular distribution of CTLA-4, interleukin-2 production, and, as a consequence, T-cell proliferation. The aim of this study was to analyze the only coding SNP CTLA-4 +49 A/G polymorphism in patients with either infectious (Chagas's, Dengue, and American cutaneous leishmaniasis) or autoimmune diseases (myasthenia gravis, pemphigus, and psoriasis). No statistically significant differences were reported when all patients of each disease group were compared with healthy individuals. However, the +49 G/G genotype was moderately increased in pemphigus and myasthenia gravis. Patients with diffuse cutaneous leishmaniasis (DCL) exhibited an increased frequency of the A/G +49 genotype compared with patients with localized cutaneous leishmaniasis (LCL; p = 0.009; odds ratio [OR] = 4.25; 95% confidence interval [CI] = 1.245-14.501) and intermediate cutaneous leishmaniasis (ICL; p = 0.027; OR = 4.44; 95% CI = 1.273-15.516), indicating that the heterozygous genotype, associated with overactivation of T-cell proliferation, could confer susceptibility to the development of the more severe clinical form of cutaneous leishmaniasis. The A/A +49 genotype was increased in LCL patients compared with DCL patients (p = 0.019; OR = 0.25; 95% CI = 0.067-0.953), indicating that this genotype, which has been associated with normal proliferation of T cells, could confer protection to the development of DCL. The results indicate that the polymorphism of CTLA-4 is an important genetic factor associated with risk or protection for the development of diffuse cutaneous leishmaniasis and has influence in the pathogenesis of autoimmune diseases. However, other closely linked candidate genes in linkage disequilibrium with CTLA4, such as CD28 and ICOS, could be associated with the development of autoimmune and infectious disease.
Assuntos
Antígenos CD/genética , Doenças Autoimunes/genética , Doenças Transmissíveis/genética , Polimorfismo de Nucleotídeo Único , Alelos , Antígeno CTLA-4 , Doença de Chagas/genética , Dengue/genética , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Humanos , Leishmaniose Cutânea/genética , Miastenia Gravis/genética , Pênfigo/genética , Psoríase/genética , Fatores de RiscoRESUMO
Three different Venezuelan Amerindian tribes were studied for human leukocyte antigen (HLA)-DPA1 and DPB1 allelic variability using polymerase chain reaction-sequence-specific oligonucleotide probes (PCR-SSOP) and sequence-based typing in a selected group of samples. These tribes are geographically (two from the Perija Mountain range and one from the Orinoco Delta) and linguistically distinct: the Bari (from Campo Rosario and Saymaidoyi villages) and the Warao have been classified within the Chibcha linguistic family, whereas the Yucpa (from the Aroy, Marewa, and Peraya villages) are Carib speaking. Venezuelan Indians, like other Native American tribes, show a markedly reduced number of different HLA-DP alleles (range, 2-7) and haplotypes (range, 4-11) in comparison with neighboring Venezuelan mestizo and other non-Indian populations. Some HLA-DPB1 (*0402 and *1401) alleles characteristic for all Amerindian tribes are present also in these populations. Despite general similarities, each tribe and, in some cases, some subtribes show their own pattern of allele and haplotype distribution apparently more as a result of linguistic than to geographic variation.
