Open AccessTumor necrosis factor promoter polymorphism TNF*‐857 is a risk allele for psoriatic arthritis independent of the PSORS1 locus
Author(s) -
Giardina Emiliano,
Hüffmeier Ulrike,
Ravindran Jaya,
Behrens Frank,
Lepre Tiziana,
McHugh Neil J.,
Korendowych Eleanor,
Burkhardt Harald,
Novelli Giuseppe,
Reis André
Publication year - 2011
Publication title -
arthritis & rheumatism
Language(s) - English
Resource type - Journals
eISSN - 1529-0131
pISSN - 0004-3591
DOI - 10.1002/art.30591
Subject(s) - allele , psoriatic arthritis , psoriasis , linkage disequilibrium , genotyping , immunology , locus (genetics) , tumor necrosis factor alpha , major histocompatibility complex , haplotype , biology , genetics , medicine , genotype , gene , antigen
Objective The strongest susceptibility locus of psoriatic arthritis (PsA) is within the major histocompatibility complex (MHC) region (psoriasis susceptibility region 1, or PSORS1 ), and HLA–Cw*06:02 has been reported as the PSORS1 susceptibility allele. Non‐HLA genes within the MHC region have also been implicated in PsA, but because of the strong linkage disequilibrium at chromosome 6p21, it is difficult to make a distinction between susceptibility alleles and linked markers. Recent studies have demonstrated that the association between PsA and the tumor necrosis factor (TNF) promoter polymorphism TNF*‐857 is independent of PSORS1 . The aim of this study was to replicate the independent association of TNF*‐857 in patients with PsA. Methods A total of 909 patients with PsA and 1,315 healthy controls originating from the UK, Germany, and Italy were typed for TNF*‐857 and for the estimated risk alleles of HLA–Cw*06:02 . Results Overall, the results of genotyping in these 3 case–control cohorts replicated the finding that the frequency of carriers of TNF*‐857 TT/CT who were negative for the PSORS1 risk allele was significantly higher among patients with PsA compared with control subjects (30% versus 21%; P = 9.17 × 10 −5 ). Conclusion The results of this collaborative study indicate that TNF*‐857T is a susceptibility allele for PsA independent of the PSORS1 allele.