Ann Rheum Dis 64:587-593 doi:10.1136/ard.2004.026831
  • Extended report

A family based study shows no association between rheumatoid arthritis and the PADI4 gene in a white French population

  1. L Caponi1,
  2. E Petit-Teixeira2,
  3. M Sebbag3,
  4. F Bongiorni4,
  5. S Moscato4,
  6. F Pratesi4,
  7. C Pierlot2,
  8. J Osorio2,
  9. S Chapuy-Regaud3,
  10. M Guerrin3,
  11. F Cornelis5,
  12. G Serre3,
  13. P Migliorini4,
  14. for ECRAF*
  1. 1Department of Experimental Pathology, University of Pisa, Pisa, Italy
  2. 2GenHotel, University Paris 7, Evry-Genopole, France
  3. 3Unit of Epidermal Differentiation and Rheumatoid Autoimmunity, UMR 5165 CNRS-Toulouse III University, Toulouse, France
  4. 4Clinical Immunology Unit, Department of Internal Medicine, University of Pisa
  5. 5Clinical Genetics Unit, Hôpital Lariboisière, Assistance Publique/Hôpitaux de Paris, Paris, France
  1. Correspondence to:
    Dr Paola Migliorini
    Clinical Immunology Unit, Department of Internal Medicine, University of Pisa, via Roma 67, I-56126 Pisa, Italy;
  • Accepted 12 August 2004
  • Published Online First 14 October 2004


Background: Autoantibodies to citrullinated proteins (ACPA) are considered a specific marker for rheumatoid arthritis. Peptidylarginine deiminase (PAD) is the enzyme that converts arginyl into citrullyl residues; different isoforms of the enzyme are expressed in mammals. It has been suggested that the PADI4 gene may contribute to genetic susceptibility to rheumatoid arthritis, but conflicting results have been obtained in different populations.

Objective: To test the hypothesis that the PADI4 gene may confer susceptibility to rheumatoid arthritis in a white French population, using powerful and highly reliable family based association tests.

Methods: DNA samples were analysed from 100 families where one member was affected by rheumatoid arthritis and both parents were available for sampling. Five single nucleotide polymorphisms, located within the PADI4 gene and in its close proximity, were genotyped by restriction fragment length polymorphism, and haplotypes were constructed. The analysis involved use of the transmission disequilibrium test and genotype relative risk. ACPA were detected by ELISA on cyclic citrullinated peptides and on human deiminated fibrinogen.

Results: No single SNP or haplotype was associated with the disease, or was preferentially transmitted. No association was found when patients were partitioned according to ACPA positivity.

Conclusions: No PADI4 haplotype is associated with rheumatoid arthritis in a white French population. The role of genes encoding the other PAD isoforms, or modulating tissue expression or enzyme activity, remains to be elucidated.


  • * Members of ECRAF are given at the end of the article