Tumor necrosis factor promoter polymorphism TNF*-857 is a risk allele for psoriatic arthritis independent of the PSORS1 locus

Authors

  • Emiliano Giardina,

    1. University of Rome Tor Vergata and Fondazione Policlinico Tor Vergata, Rome, Italy
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    • Drs. Giardina, Hüffmeier, Behrens, Lepre, McHugh, Korendowych, Burkhardt, Novelli, and Reis are members of the Psoriatic Arthritis Genetics European Consortium.

  • Ulrike Hüffmeier,

    1. University of Erlangen–Nuremberg, Erlangen, Germany
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    • Drs. Giardina, Hüffmeier, Behrens, Lepre, McHugh, Korendowych, Burkhardt, Novelli, and Reis are members of the Psoriatic Arthritis Genetics European Consortium.

  • Jaya Ravindran,

    1. Royal National Hospital for Rheumatic Diseases and University of Bath, Bath, UK
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  • Frank Behrens,

    1. Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany
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    • Drs. Giardina, Hüffmeier, Behrens, Lepre, McHugh, Korendowych, Burkhardt, Novelli, and Reis are members of the Psoriatic Arthritis Genetics European Consortium.

  • Tiziana Lepre,

    1. University of Rome Tor Vergata and Fondazione Policlinico Tor Vergata, Rome, Italy
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    • Drs. Giardina, Hüffmeier, Behrens, Lepre, McHugh, Korendowych, Burkhardt, Novelli, and Reis are members of the Psoriatic Arthritis Genetics European Consortium.

  • Neil J. McHugh,

    1. Royal National Hospital for Rheumatic Diseases and University of Bath, Bath, UK
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    • Drs. Giardina, Hüffmeier, Behrens, Lepre, McHugh, Korendowych, Burkhardt, Novelli, and Reis are members of the Psoriatic Arthritis Genetics European Consortium.

  • Eleanor Korendowych,

    1. Royal National Hospital for Rheumatic Diseases and University of Bath, Bath, UK
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    • Drs. Giardina, Hüffmeier, Behrens, Lepre, McHugh, Korendowych, Burkhardt, Novelli, and Reis are members of the Psoriatic Arthritis Genetics European Consortium.

  • Harald Burkhardt,

    1. Johann Wolfgang Goethe University Hospital, Frankfurt am Main, Germany
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    • Drs. Giardina, Hüffmeier, Behrens, Lepre, McHugh, Korendowych, Burkhardt, Novelli, and Reis are members of the Psoriatic Arthritis Genetics European Consortium.

  • Giuseppe Novelli,

    Corresponding author
    1. National Agency of Evaluation of Universities and Research (ANVUR), University of Rome Tor Vergata, and Fondazione Policlinico Tor Vergata, Rome, Italy
    • University of Rome Tor Vergata, Department of Biopathology, Via Montpellier 1, 00133 Rome, Italy
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    • Drs. Giardina, Hüffmeier, Behrens, Lepre, McHugh, Korendowych, Burkhardt, Novelli, and Reis are members of the Psoriatic Arthritis Genetics European Consortium.

  • André Reis

    1. University of Erlangen–Nuremberg, Erlangen, Germany
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    • Drs. Giardina, Hüffmeier, Behrens, Lepre, McHugh, Korendowych, Burkhardt, Novelli, and Reis are members of the Psoriatic Arthritis Genetics European Consortium.


Abstract

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.

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