A TNF-alpha promoter polymorphism is associated with juvenile onset psoriasis and psoriatic arthritis

J Invest Dermatol. 1997 Oct;109(4):562-5. doi: 10.1111/1523-1747.ep12337469.

Abstract

Tumor necrosis factor-alpha is considered to be one of the important mediators in the pathogenesis of psoriasis. A strong association of juvenile onset psoriasis with the major histocompatibility complex encoded HLA-Cw6 antigen has been reported but it is unclear whether Cw6 itself or a closely linked gene is involved in the pathogenesis. This study has focused on the association of promoter polymorphisms of the major histocompatibility complex encoded tumor necrosis factor-alpha gene with psoriasis and psoriatic arthritis. Tumor necrosis factor-alpha promoter polymorphisms were sought by sequence-specific oligonucleotide hybridization and by direct sequencing in Caucasian patients with juvenile onset psoriasis and with psoriatic arthritis and in healthy controls. A mutation at position -238 of the tumor necrosis factor-alpha promoter was present in 23 of 60 patients (38%; p < 0.0001; p[corr] < 0.008) with juvenile onset psoriasis and in 20 of 62 patients (32%; p < 0.0003; p[corr] < 0.03) with psoriatic arthritis, compared with seven of 99 (7%) Caucasian controls. There was a marked increase of homozygotes for this mutation in the psoriasis group. Another mutation at position -308 was found in similar proportions of patients and controls. Our study shows a strong association of the tumor necrosis factor-alpha promoter polymorphism at position -238 with psoriasis and psoriatic arthritis. Our findings suggest that this promoter polymorphism itself or a gene in linkage disequilibrium with tumor necrosis factor-alpha predispose to the development of psoriasis.

MeSH terms

  • Adult
  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Arthritis, Psoriatic / genetics*
  • Female
  • Genetic Linkage
  • HLA-B Antigens / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Promoter Regions, Genetic / genetics*
  • Psoriasis / epidemiology
  • Psoriasis / genetics*
  • Risk Factors
  • Tumor Necrosis Factor-alpha / genetics*

Substances

  • HLA-B Antigens
  • HLA-B57 antigen
  • Tumor Necrosis Factor-alpha