title: Impact of Toll-like receptor-4 and tumour necrosis factor gene polymorphisms in patients with hidradenitis suppurativa.
abstract: BACKGROUND
  Recent evidence has suggested that deranged immune responses play a role in the pathogenesis of hidradenitis suppurativa (HS).
  
  
  OBJECTIVE
  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.
authors.affiliation: Fourth Department of Internal Medicine, ATTIKON University Hospital, 1, Rimini Str., P.C. 12462, Athens, Greece. savva.athina@gmail.com
authors.forename: A
authors.initials: A
authors.lastname: Savva
authors.forename: T
authors.initials: T
authors.lastname: Kanni
authors.forename: G
authors.initials: G
authors.lastname: Damoraki
authors.forename: A
authors.initials: A
authors.lastname: Kotsaki
authors.forename: S
authors.initials: S
authors.lastname: Giatrakou
authors.forename: I
authors.initials: I
authors.lastname: Grech
authors.forename: A
authors.initials: A
authors.lastname: Katoulis
authors.forename: E
authors.initials: E
authors.lastname: Papadavid
authors.forename: E J
authors.initials: EJ
authors.lastname: Giamarellos-Bourboulis
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D016022:Case-Control Studies; D003879:Dermatologic Agents / Q000627:therapeutic use; D000068800:Etanercept; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D017497:Hidradenitis Suppurativa / Q000188:drug therapy / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000627:therapeutic use; D000069285:Infliximab; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D018124:Receptors, Tumor Necrosis Factor / Q000627:therapeutic use; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000235:genetics*
chemical_list: D000911:Antibodies, Monoclonal; D003879:Dermatologic Agents; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab; D000068800:Etanercept