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

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:109

Article

Hohler, T ; Kruger, A ; Schneider, PM ; Schopf, RE ; Knop, J ; Rittner, C ; zumBuschenfelde, KHM ; MarkerHermann, E

关键词: cytokines;    HLA antigens;    linkage disequilibrium;    major histocompatibility complex;   

DOI  :  10.1111/1523-1747.ep12337469

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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