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The TNFRSF1A R92Q mutation is frequent in rheumatoid arthritis but shows no evidence for association or linkage with the disease
  1. Philippe Dieudé2,
  2. Michel Goossens3,
  3. François Cornélis1,
  4. Laëtitia Michou1,
  5. Thomas Bardin4,
  6. Dimitri Olegovitch Tchernitchko3,
  7. for the European Consortium on Rheumatoid Arthritis Families
  1. 1GenHotel-EA3886, Universités Evry-Paris 7, Evry-Genopole, France
  2. 2Service de Rhumatologie, Hôpital Bichat Claude Bernard, Assistance Publique des Hôpitaux de Paris, Paris, France
  3. 3Service de Biochimie et de Génétique, Hôpital Henri Mondor, Assistance Publique des Hôpitaux de Paris, Créteil, France
  4. 4Fédération de Rhumatologie, Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris, Paris, France
  1. Correspondence to:
    Philippe Dieudé
    MD-PhD, Service de Rhumatologie, Hôpital Bichat Claude Bernard, 46 rue Henri Huchard, Paris 75018, France; philippe.dieude{at}


Objective:TNFRSF1A mutations cause TNFRSF1A-associated periodic syndrome (MIM#142680). A recent study suggested that the R92Q mutation was associated with polyarthritis. We aimed to search for this and other TNFRSF1A mutations in rheumatoid arthritis (RA), and to test for linkage.

Methods: The DNA of 100 trio families and 86 index cases of RA-affected sib-pair (ASP) families from the French Caucasian population were investigated by denatured high-performance liquid chromatography for TNFRSF1A mutations in exons 2 to 4. The test for association compared cases and controls (derived from un-transmitted parental chromosomes). The test for linkage relied on the transmission disequilibrium test (TDT) in trio families and cosegregation in ASP families.

Results: Only the R92Q mutation was detected – in 2 of the 100 index cases of trio families and in 5 (5.8%) of the index cases of ASP families, but also in 5% of the controls, showing no association with the disease. No RA linkage evidence was found in TDT and ASP RA families.

Conclusion: This TNFRSF1A investigation in RA from the French Caucasian population showed only the R92Q mutation, with a frequency of 4.5%, but no evidence for RA association or linkage to the disease. The R92Q mutation could be considered to be a low-penetrance variant.

  • dHPLC, denatured high-performance liquid chromatography
  • GRR, genotype relative risk
  • RA, rheumatoid arthritis
  • TDT, Transmission Disequilibrium Test
  • TNFR, tumour necrosis factor receptor
  • TRAPS, TNFRSF1A-associated periodic syndrome
  • TNFRSF1A, rheumatoid arthritis, TRAPS, TNFR, R92Q mutation

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  • Competing interests: None declared.

  • Published Online First 26 January 2007