Linkage proof for PTPN22, a rheumatoid arthritis susceptibility gene and a human autoimmunity gene

• Type: Article in International Scientific Journal
• Date: 2007

Authors

Laetitia Michou (Author) Other; Sandra Lasbleiz (Author) Other; Anne-Christine Rat (Author) Other; Paola Migliorini (Author) Other; Alejandro Balsa (Author) Other; René Westhovens (Author) Other; Pilar Barrera (Author) Other; Helena Alves (Author) Other; Céline Pierlot (Author) Other; Elodie Glikmans (Author) Other; Sophie Garnier (Author) Other; Jean Dausset (Author) Other; Carlos Vaz (Author) FMUP; Manuela Fernandes (Author) Other; Elisabeth Petit-Teixeira (Author) Other; Isabelle Lemaire (Author) Other; Dora Pascual-Salcedo (Author) Other; Stefano Bombardieri (Author) Other; Jan Dequeker (Author) Other; Timothy Radstake (Author) Other; Piet Riel (Author) Other; Leo Putte (Author) Other; António Lopes-Vaz (Author) Other; Bernard Prum (Author) Other; Thomas Bardin (Author) Other; Philippe Dieudé (Author) Other; François Cornélis (Author) Other

Journal

Title: Proceedings of the National Academy of Sciences of the United States of America

Vol. 104 No. 5

Pages: 1649-1654

ISSN: 0027-8424

Publisher: National Academy of Sciences

Indexing

ISI Web of Knowledge - 71 Citations

Scopus - 86 Citations

Pubmed / Medline

Scientific classification

CORDIS: Health sciences > Medical sciences > Medicine

Other information

Authenticus ID: P-004-C6W

DOI: 10.1073/pnas.0610250104

Abstract (EN): 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 approximate to 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 TIC) 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 approximate to 1% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 6