Tumor necrosis factor polymorphisms in psoriatic arthritis : association with the promoter polymorphism TNF-857 independent of the PSORS1 risk allele

  • Poster presentation Background Single nucleotide polymorphisms (SNPs) of the TNF gene at positions -238 and -308 have earlier been associated with psoriasis vulgaris and psoriatic arthritis (PsA). However, a strong linkage disequilibrium at the chromosomal region 6p21 renders the interpretation of these findings difficult since also other risk factors for psoriasis (PSORS1) than SNPs of the TNF gene have bee mapped to that particular region. Therefore, in this study several SNPs of the TNF gene and of its neighbouring lymphotoxin alpha (LTA) gene were analysed independently and dependently on carrying the PSORS1 risk allele. Methods SNPs in the promoter of the TNF gene (-238G/A, -308G/A, -857C/T, -1031T/C), and one SNP of the LTA gene (+252A/G), of the TNLFRSF1A gene (+36A/G) and of the TNLFRSF1B gene (+676T/G), respectively, were genotyped in 375 psoriasis patients, 375 PsA patients, and 376 controls. The tryptophan–tryptophan–cysteine–cysteine haplotype of the CCHCR1 gene (CCHCR1*WWCC) was used to estimate the genetic impact of the PSORS1 risk allele. Results Whereas an earlier-described association of allele TNF*-238A with psoriasis could be confirmed, our study revealed that this association was completely dependent on concomitant carriage of the PSORS1 risk allele. For PsA, but not psoriasis vulgaris without joint manifestations, strong association with the allele TNF*-857T was detected (OR = 1.956; P value corrected for multiple testing, Pcorr = 0.0025) also in patients negative for the PSORS1 risk allele. Conclusion Our results indicate genetic differences between psoriasis vulgaris patients with and without joint manifestation. While the previously reported association between TNF*-238A and psoriasis seems to primarily reflect linkage disequilibrium with PSORS1, TNF*-857T may represent a risk factor for PsA independent of PSORS1. A potential pathophysiologic relevance of the elucidated genetic association is further suggested by previously reported experimental evidence for a functional impact of the respective TNF polymorphism on TNFalpha expression levels.

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Author:Kristian ReichORCiDGND, Ulrike Hüffmeier, Inke R. König, Jesús Lascorz, Jörg Lohmann, Jörg Wendler, Heiko Traupe, Rotraut Mössner, André ReisORCiDGND, Harald BurkhardtORCiDGND
Parent Title (German):Arthritis Research & Therapy
Document Type:Article
Year of Completion:2007
Year of first Publication:2007
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2007/10/22
Issue:(Suppl 3):P18
© 2007 BioMed Central Ltd ;  6th Global Arthritis Research Network (GARN) Meeting
Source:Arthritis Research & Therapy 2007, 9(Suppl 3):P18 (doi:10.1186/ar2244). - http://arthritis-research.com/content/9/S3/P18
Institutes:Medizin / Medizin
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoDeutsches Urheberrecht