Author(s): Savva A, Kanni T, Damoraki G, Kotsaki A, Giatrakou S, Grech I, Katoulis A, Papadavid E, Giamarellos-Bourboulis EJ
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.
Dermatology Journal and/or Publisher
Journal Name: The British journal of dermatology
Journal Abbreviation: Br. J. Dermatol.
Journal Date Published: 2013-01-31
National Center for Biotechnology Information
Article Source: http://www.ncbi.nlm.nih.gov/pubmed/23106544
Lasted Revision: 2015-11-19
Abstract Source: National Center for Biotechnology Information, U.S. National Library of Medicine Abstract Query for Hidradenitis suppurativa (HS).