A TNF-alpha promoter polymorphism is associated with juvenile onset psoriasis and psoriatic arthritis.
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.
Höhler
T
T
I. Medical Department, Johannes Gutenberg Universität Mainz, Germany.
Kruger
A
A
Schneider
P M
PM
Schopf
R E
RE
Knop
J
J
Rittner
C
C
Meyer zum Büschenfelde
K H
KH
Märker-Hermann
E
E
D000328:Adult; D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D015535:Arthritis, Psoriatic / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage; D015235:HLA-B Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D015235:HLA-B Antigens; C103707:HLA-B57 antigen; D014409:Tumor Necrosis Factor-alpha