Linkage Proof for PTPN22, a Rheumatoid Arthritis Susceptibility Gene and a Human Autoimmunity Gene - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Proceedings of the National Academy of Sciences of the United States of America Année : 2007

Linkage Proof for PTPN22, a Rheumatoid Arthritis Susceptibility Gene and a Human Autoimmunity Gene

Paola Migliorini
  • Fonction : Auteur
René Westhovens
Pilar Barrera
  • Fonction : Auteur
Helena Alves
  • Fonction : Auteur
Jean Dausset
  • Fonction : Auteur
  • PersonId : 834948
Carlos Vaz
  • Fonction : Auteur
Manuela Fernandes
  • Fonction : Auteur
Dora Pascual-Salcedo
  • Fonction : Auteur
Stefano Bombardieri
  • Fonction : Auteur
Jan Dequeker
  • Fonction : Auteur
Timothy R. Radstake
  • Fonction : Auteur
Piet van Riel
  • Fonction : Auteur
Leo van De Putte
  • Fonction : Auteur
Antonio Lopes-Vaz
  • Fonction : Auteur
Bernard Prum
  • Fonction : Auteur
  • PersonId : 899353

Résumé

The tyrosine phosphatase PTPN22 allele 1858T has been associated with rheumatoid arthritis (RA) and other autoimmune diseases. RA is the most frequent of those multifactorial diseases. The RA association was usually restricted to serum rheumatoid factor positive disease (RF+). No interaction was shown with HLA-DRB1, the first RA gene. Many case-control studies replicated the RA association, showing an allele frequency increase of approximately 5% on average and large variations of population allele frequencies (2.1-15.5%). In multifactorial diseases, the final proof for a new susceptibility allele is provided by departure from Mendel's law (50% transmission from heterozygous parents). For PTPN22-1858T allele, convincing linkage proof was available only for type 1 diabetes. We aimed at providing this proof for RA. We analyzed 1,395 West European Caucasian individuals from 465 "trio" families. We replicated evidence for linkage, demonstrating departure from Mendel's law in this subset of early RA onset patients. We estimated the overtransmission of the 1858T allele in RF+ families: T = 63%, P \backslashtextless 0.0007. The 1858T allele frequency increased from 11.0% in controls to 17.4% in RF+ RA for the French Caucasian population and the susceptibility genotype (1858T/T or T/C) from 20.2% to 31.6% [odds ratio (OR) = 1.8 (1.2-2.8)]. In conclusion, we provided the linkage proof for the PTPN22-1858T allele and RF+ RA. With diabetes and RA, PTPN22 is therefore a "linkage-proven" autoimmunity gene. PTPN22 accounting for approximately 1% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases.

Dates et versions

hal-02084378 , version 1 (29-03-2019)

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Citer

Laëtitia Michou, Sandra Lasbleiz, Anne-Christine Rat, Paola Migliorini, Alejandro Balsa, et al.. Linkage Proof for PTPN22, a Rheumatoid Arthritis Susceptibility Gene and a Human Autoimmunity Gene. Proceedings of the National Academy of Sciences of the United States of America, 2007, 104 (5), pp.1649--1654. ⟨10.1073/pnas.0610250104⟩. ⟨hal-02084378⟩
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