RESUMEN
BACKGROUND: Recent evidence has suggested that deranged immune responses play a role in the pathogenesis of hidradenitis suppurativa (HS). OBJECTIVES: To investigate the role of single nucleotide polymorphisms (SNPs) of the tumour necrosis factor (TNF) and Toll-like receptor 4 (TLR4) genes in the physical course of HS; these genes encode for proteins implicated in the immune response of the host. METHODS: DNA was isolated from 190 patients with HS and 84 healthy controls. SNPs at the promoter regions -376G/A, -238G/A and -308G/A of the TNF gene and the Asp299Gly and Thr399Ile SNPs of the TLR4 gene were determined by polymerase chain reaction (PCR) and digestion of the PCR product by restriction enzymes; after electrophoresis on 2·0% agarose gel, products were visualized on under ultraviolet radiation. RESULTS: The presence of the -238 TNF gene polymorphism was associated with a predisposition to HS (P = 0·027). Susceptibility to the disease was strongly correlated with the presence of AGG/GGA/AGA/GAA TNF haplotypes in 32 (17%) patients compared with two (2%) controls (P < 0·001, odds ratio 8·30, 95% confidence interval 1·94-35·52). The frequency of HS exacerbations and disease severity were greater in patients carrying any of the GAG/AGG/GGA/AGA/GAA haplotypes of the TNF gene. Thirty-two patients were given TNF antagonists. Nineteen of these patients were carriers of the GGG haplotype of the TNF gene, whereas 13 were carriers of other haplotypes; favourable responses as evidenced by the Sartorius score were registered in 15 (79%) and five (38%, P = 0·025), respectively. Carriage of the TLR4 gene alleles was not associated with any disease parameter. CONCLUSIONS: A significant role of SNPs at the promoter region of the TNF gene is indicated for susceptibility to HS and for response to TNF antagonists.
Asunto(s)
Hidradenitis Supurativa/genética , Polimorfismo de Nucleótido Simple/genética , Receptor Toll-Like 4/genética , Factor de Necrosis Tumoral alfa/genética , Adulto , Anticuerpos Monoclonales/uso terapéutico , Estudios de Casos y Controles , Fármacos Dermatológicos/uso terapéutico , Etanercept , Femenino , Predisposición Genética a la Enfermedad/genética , Genotipo , Haplotipos , Hidradenitis Supurativa/tratamiento farmacológico , Hidradenitis Supurativa/inmunología , Humanos , Inmunoglobulina G/uso terapéutico , Infliximab , Masculino , Reacción en Cadena de la Polimerasa , Regiones Promotoras Genéticas/genética , Estudios Prospectivos , Receptores del Factor de Necrosis Tumoral/uso terapéutico , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresRESUMEN
BACKGROUND: Former studies have shown that Propionibacterium acnes may stimulate expression of toll-like receptor 4 (TLR4) in keratinocytes of patients with acne vulgaris. OBJECTIVE: To investigate the impact of single nucleotide polumorphisms (SNPs) of the TLR4 gene in acne vulgaris. METHODS: Genomic DNA was isolated from 191 patients with acne vulgaris and 75 healthy controls. Asp299Gly and Thr399Ile SNPs were defined after cutting of the PCR products by restriction enzymes. Sebum of lesions was cultured for P. acnes. RESULTS: No differences in SNP allele frequencies were found between patients and healthy controls. 46.5% of carriers of wild-type alleles were suffering from acne conglobata compared with 28.6% of carriers of SNP alleles (P=0.040). After adjusting for gender, family history of acnes, intake of any therapy and skin isolation of P. acnes, carriage of TLR4 gene SNPs was the only independent variable linked with a protective role against acne conglobata (OR=0.269, P=0.014). No differences were found in the amount of pro-inflammatory cytokines released by peripheral blood mononuclear cells isolated from patients with acne conglobata carrying only wild-type alleles and SNP alleles. CONCLUSIONS: Carriage of gene SNPs is protective against the development of acne conglobata even in the presence of P. acnes.