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.
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.
Authors: Philip E Stuart; Rajan P Nair; Lam C Tsoi; Trilokraj Tejasvi; Sayantan Das; Hyun Min Kang; Eva Ellinghaus; Vinod Chandran; Kristina Callis-Duffin; Robert Ike; Yanming Li; Xiaoquan Wen; Charlotta Enerbäck; Johann E Gudjonsson; Sulev Kõks; Külli Kingo; Tõnu Esko; Ulrich Mrowietz; Andre Reis; H Erich Wichmann; Christian Gieger; Per Hoffmann; Markus M Nöthen; Juliane Winkelmann; Manfred Kunz; Elvia G Moreta; Philip J Mease; Christopher T Ritchlin; Anne M Bowcock; Gerald G Krueger; Henry W Lim; Stephan Weidinger; Michael Weichenthal; John J Voorhees; Proton Rahman; Peter K Gregersen; Andre Franke; Dafna D Gladman; Gonçalo R Abecasis; James T Elder Journal: Am J Hum Genet Date: 2015-11-28 Impact factor: 11.025