Title: Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene
Authors: Michou, Laëtitia ×
Lasbleiz, Sandra
Rat, Anne-Christine
Migliorini, Paola
Balsa, Alejandro
Westhovens, René
Barrera, Pilar
Alves, Helena
Pierlot, Céline
Glikmans, Elodie
Garnier, Sophie
Dausset, Jean
Vaz, Carlos
Fernandes, Manuela
Petit-Teixeira, Elisabeth
Lemaire, Isabelle
Pascual-Salcedo, Dora
Bombardieri, Stefano
Dequeker, Jan
Radstake, Timothy R
Van Riel, Piet
van de Putte, Leo
Lopes-Vaz, Antonio
Prum, Bernard
Bardin, Thomas
Dieudé, Philippe
Cornélis, François #
Issue Date: 9-Jan-2007
Series Title: Proceedings of the National Academy of Sciences of the United States of America vol:104 issue:5 pages:1649-54
Abstract: 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 < 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.
ISSN: 0027-8424
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Rheumatology Section (-)
Faculty of Medicine - miscellaneous
× corresponding author
# (joint) last author

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