Impact of Toll‐like receptor‐4 and tumour necrosis factor gene polymorphisms in patients with hidradenitis suppurativa. (30th January 2013)

• Record Type: Journal Article
• Authors: Savva, A.; Kanni, T.; Damoraki, G.; Kotsaki, A.; Giatrakou, S.; Grech, I.; Katoulis, A.; Papadavid, E.; Giamarellos‐Bourboulis, E.J.
• Is Part Of: British journal of dermatology. Volume 168:Number 2(2013:Feb.)
• Page Start: 311
• Page End: 317
• Publication Date: 2013-01-30
• Subjects: Dermatology -- Periodicals; Skin -- Diseases -- Periodicals; 616.5
• DOI: 10.1111/bjd.12105
• Languages: English
• ISSNs: 0007-0963

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Summary</title> <p> <bold>Background </bold> Recent evidence has suggested that deranged immune responses play a role in the pathogenesis of hidradenitis suppurativa (HS).</p> <p> <bold>Objectives </bold> To investigate the role of single nucleotide polymorphisms (SNPs) of the tumour necrosis factor (<italic>TNF</italic>) and Toll‐like receptor 4 (<italic>TLR4</italic>) genes in the physical course of HS; these genes encode for proteins implicated in the immune response of the host.</p> <p> <bold>Methods </bold> 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 <italic>TNF</italic> gene and the Asp299Gly and Thr399Ile SNPs of the <italic>TLR4</italic> 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.</p> <p> <bold>Results </bold> The presence of the −238 <italic>TNF</italic> gene polymorphism was associated with a predisposition to HS (<italic>P = </italic>0·027). Susceptibility to the disease was strongly correlated with the presence of AGG/GGA/AGA/GAA <italic>TNF</italic> haplotypes in 32 (17%) patients compared with two (2%) controls (<italic>P </italic><<italic> </italic>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 <italic>TNF</italic> gene. Thirty‐two patients were given TNF antagonists. Nineteen of these patients were carriers of the GGG haplotype of the <italic>TNF</italic> gene, whereas 13 were carriers of other haplotypes; favourable responses as evidenced by the Sartorius score were registered in 15 (79%) and five (38%, <italic>P </italic>=<italic> </italic>0·025), respectively. Carriage of the <italic>TLR4</italic> gene alleles was not associated with any disease parameter.</p> <p> <bold>Conclusions </bold> A significant role of SNPs at the promoter region of the <italic>TNF</italic> gene is indicated for susceptibility to HS and for response to TNF antagonists.</p> </abstract>