A TNF-α Promoter Polymorphism Is Associated with Juvenile Onset Psoriasis and Psoriatic Arthritis

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.

Association of the TNF +489 polymorphism with susceptibility and radiographic damage in rheumatoid arthritis

“…12 Hence, variations in the capacity to produce TNF may be related to susceptibility and outcome of autoimmune and infectious diseases. The associations of TNF −238 alleles with disease outcome in other diseases like psoriasis and psoriatic arthritis, 39 SLE, 37 scarring thrachoma 40 and alcoholic steatohepatitis 41 has strengthened the speculation of functionality of TNF gene polymorphisms. However, functional analysis of the −238 polymorphism has not provided evidence for functional relevance of this TNF gene variant.…”

Laboratory Findings in Psoriatic Arthritis

“…This observation is in keeping with the crucial role that inflammatory cytokines play in PsA (22), probably related with genetic predisposition. TNF-α promoter polymorphism or a gene in linkage disequilibrium with TNF-α may also contribute to confer predisposition or increase susceptibility to psoriasis and PsA (23). One study looking at the TNFβ+252 and TNFα-308 polymorphisms did not find any differences in allele frequencies between PsA patients and matched controls, however both polymorphisms were significantly associated with the presence of joint erosions and the progression of joint erosions in early PsA (24).…”

Distinct Cytokine Profiles in Patients with Oligoarticular Juvenile Idiopathic Arthritis after &lt;i&gt;in&lt;/i&gt; &lt;i&gt;Vitro&lt;/i&gt; Blockade of Interleukin (IL)-1 and Tumor Necrosis Factor (TNF)-α

“…In addition, the −308G genotype has been associated with better response to anti-TNF-α treatment in JIA patients, confirming adult data [17]. In some studies oligoarticular arthritis is significantly associated to the −238 SNP [10] [16] [18] [19].…”