Caracterização do polimorfismo dos alelos HLA de classe I e nos microssatelites do fator de necrose tumoral em pacientes brasileiros com psoriase vulgar

AUTOR(ES)
DATA DE PUBLICAÇÃO

2005

RESUMO

Introduction - Psoriasis is a genetic chronic inflammatory skin disorder with genes involved in disease predisposition located within the highly polymorphic Major Histocompatibility Complex (MHC) region on the chromosome 6p21.3. The goal of the present study was to identify, evaluate distribution and determine genetic associations of HLA class I genes and Tumor Necrosis Factor (TNF) microsatellites with psoriasis in Brazilian patients. Patients and Methods - HLA-A,-B, -C typingwas carriedout in 92 psoriasispatientsand 160 healthy individuaIs through genomic DNA using the PCR-SSP method. Typing ofTNF microsatellites was carried out in 70 of the 92 psoriasis patients and in 71 healthy controls. TNF microsatellites were classified according to the number of alleles (TNFa, b, c, d, e) amplified through genomic DNA by polymerase chain reaction and visualized in denaturing polyacrylamine gel, in specific conditions for each locus. Results - Of the 92 patients, 43.3% were HLA-Cw*06 positive (p<0.0001 and OR=5.3). HLA-B*13, HLA-B*57, HLA-Cw*12 alleles and HLA-B*13 Cw*06, HLA-B*57 Cw*06 and HLA-B*39 Cw*12 haplotypes were found to be increased in patients with psoriasis, with a statistical significance (p<0.05) when compared to healthy individuaIs. TNFa4, TNFbl, TNFel microsatellites and the TNFa2 bl c2 d4 el haplotype showed a decreased frequency and a statistical significance (p<0.05) in psoriasis patients when compared to healthy individuals. HLA-B*13 allele and HLA-B*13 Cw*06, TNFall b4 c1 d3 e3 haplotypes showed increased frequencies and a statistical significance (p<0.05) in patients with type II psoriasis when compared to healthy individuaIs. We further found an extended haplotype in that chromosomic region, HLA-B*57 HLA-Cw*06 TNFa2 b5 c2 d4 c3, with a statistical significance (p<0.05). Conclusions - This study shows a positive association between the HLA-B*13, HLA-B*57, Cw*06, Cw*12 alleles and the B*13 Cw*06, B*57 Cw*06, B*39 Cw*12, TNFall b4 cl d3 e3 haplotypes and the extended haplotype HLA-B*57 Cw*06 TNFa2 b5 c2 d4 e3, which determines susceptibility to the development ofpsoriasis. We further found TNFa4, TNFbl, TNFel microsatellites and the TNFa2 bl c2 d4 el haplotype with negative association, which suggests a protection factor against psoriasis. Results point to the fact that detection of HLA class I polymorphisms and microsatellites in the TNF locus may be markers of either genetic susceptibility, or protection against the disease in Brazilian patients

ASSUNTO(S)

complexo principal de histocompatibilidade susceptibilidade a doença psoriase

ACESSO AO ARTIGO

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