{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T01:27:27Z","timestamp":1774315647448,"version":"3.50.1"},"reference-count":45,"publisher":"Proceedings of the National Academy of Sciences","issue":"5","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2007,1,30]]},"abstract":"<jats:p>\n            The tyrosine phosphatase\n            <jats:italic>PTPN22<\/jats:italic>\n            allele\n            <jats:italic>1858T<\/jats:italic>\n            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\n            <jats:sup>+<\/jats:sup>\n            ). No interaction was shown with\n            <jats:italic>HLA-DRB1<\/jats:italic>\n            , the first RA gene. Many case-control studies replicated the RA association, showing an allele frequency increase of \u22485% on average and large variations of population allele frequencies (2.1\u201315.5%). 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\n            <jats:italic>PTPN22\u20131858T<\/jats:italic>\n            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 \u201ctrio\u201d 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\n            <jats:italic>1858T<\/jats:italic>\n            allele in RF\n            <jats:sup>+<\/jats:sup>\n            families:\n            <jats:italic>T<\/jats:italic>\n            = 63%,\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0007. The\n            <jats:italic>1858T<\/jats:italic>\n            allele frequency increased from 11.0% in controls to 17.4% in RF\n            <jats:sup>+<\/jats:sup>\n            RA for the French Caucasian population and the susceptibility genotype (\n            <jats:italic>1858T<\/jats:italic>\n            \/\n            <jats:italic>T<\/jats:italic>\n            or\n            <jats:italic>T<\/jats:italic>\n            \/\n            <jats:italic>C<\/jats:italic>\n            ) from 20.2% to 31.6% [odds ratio (OR) = 1.8 (1.2\u20132.8)]. In conclusion, we provided the linkage proof for the\n            <jats:italic>PTPN22\u20131858T<\/jats:italic>\n            allele and RF\n            <jats:sup>+<\/jats:sup>\n            RA. With diabetes and RA,\n            <jats:italic>PTPN22<\/jats:italic>\n            is therefore a \u201clinkage-proven\u201d autoimmunity gene.\n            <jats:italic>PTPN22<\/jats:italic>\n            accounting for \u22481% of the RA familial aggregation, many new genes could be expected that are as many leads to definitive therapy for autoimmune diseases.\n          <\/jats:p>","DOI":"10.1073\/pnas.0610250104","type":"journal-article","created":{"date-parts":[[2007,1,20]],"date-time":"2007-01-20T01:40:22Z","timestamp":1169257222000},"page":"1649-1654","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":84,"title":["Linkage proof for\n            <i>PTPN22<\/i>\n            , a rheumatoid arthritis susceptibility gene and a human autoimmunity gene"],"prefix":"10.1073","volume":"104","author":[{"given":"La\u00ebtitia","family":"Michou","sequence":"first","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"},{"name":"F\u00e9d\u00e9ration de Rhumatologie, P\u00f4le de l'Appareil Locomoteur, Lariboisi\u00e8re Hospital, AP-HP, 2 Rue Ambroise Par\u00e9, 75010 Paris, France;"}]},{"given":"Sandra","family":"Lasbleiz","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"},{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Clinique, P\u00f4le des Laboratoires M\u00e9dicaux-Imagerie-Pharmacie, Lariboisi\u00e8re Hospital, AP-HP, 2 Rue Ambroise Par\u00e9, 75010 Paris, France;"}]},{"given":"Anne-Christine","family":"Rat","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"}]},{"given":"Paola","family":"Migliorini","sequence":"additional","affiliation":[{"name":"Pisa University, 56126 Pisa, Italy;"}]},{"given":"Alejandro","family":"Balsa","sequence":"additional","affiliation":[{"name":"La Paz Hospital, 28046 Madrid, Spain;"}]},{"given":"Ren\u00e9","family":"Westhovens","sequence":"additional","affiliation":[{"name":"Katholieke Universiteit Leuven, BE-3000 Leuven, Belgium;"}]},{"given":"Pilar","family":"Barrera","sequence":"additional","affiliation":[{"name":"Nijmegen University, 6500HB Nijmegen, The Netherlands;"}]},{"given":"Helena","family":"Alves","sequence":"additional","affiliation":[{"name":"Porto San Joao Hospital, 4200 Porto, Portugal;"}]},{"given":"C\u00e9line","family":"Pierlot","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"}]},{"given":"Elodie","family":"Glikmans","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"}]},{"given":"Sophie","family":"Garnier","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"}]},{"given":"Jean","family":"Dausset","sequence":"additional","affiliation":[{"name":"Fondation Jean Dausset, Centre d'\u00c9tude du Polymorphisme Humain, 27 Rue Juliette Dodu, 75010 Paris, France;"}]},{"given":"Carlos","family":"Vaz","sequence":"additional","affiliation":[{"name":"Porto San Joao Hospital, 4200 Porto, Portugal;"}]},{"given":"Manuela","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Porto San Joao Hospital, 4200 Porto, Portugal;"}]},{"given":"Elisabeth","family":"Petit-Teixeira","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"}]},{"given":"Isabelle","family":"Lemaire","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"},{"name":"Service de Biologie, Centre Hospitalier Sud Francilien, 59 Boulevard H. Dunant, 91106 Evry-Corbeil, France;"}]},{"given":"Dora","family":"Pascual-Salcedo","sequence":"additional","affiliation":[{"name":"La Paz Hospital, 28046 Madrid, Spain;"}]},{"given":"Stefano","family":"Bombardieri","sequence":"additional","affiliation":[{"name":"Pisa University, 56126 Pisa, Italy;"}]},{"given":"Jan","family":"Dequeker","sequence":"additional","affiliation":[{"name":"Katholieke Universiteit Leuven, BE-3000 Leuven, Belgium;"}]},{"given":"Timothy R.","family":"Radstake","sequence":"additional","affiliation":[{"name":"Nijmegen University, 6500HB Nijmegen, The Netherlands;"}]},{"given":"Piet","family":"Van Riel","sequence":"additional","affiliation":[{"name":"Nijmegen University, 6500HB Nijmegen, The Netherlands;"}]},{"given":"Leo","family":"van de Putte","sequence":"additional","affiliation":[{"name":"Nijmegen University, 6500HB Nijmegen, The Netherlands;"}]},{"given":"Antonio","family":"Lopes-Vaz","sequence":"additional","affiliation":[{"name":"Porto San Joao Hospital, 4200 Porto, Portugal;"}]},{"given":"Bernard","family":"Prum","sequence":"additional","affiliation":[{"name":"Laboratoire Statistique et G\u00e9nome, Centre National de la Recherche Scientifique, Evry University, 91000 Evry-Genopole, France;"}]},{"given":"Thomas","family":"Bardin","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"},{"name":"F\u00e9d\u00e9ration de Rhumatologie, P\u00f4le de l'Appareil Locomoteur, Lariboisi\u00e8re Hospital, AP-HP, 2 Rue Ambroise Par\u00e9, 75010 Paris, France;"}]},{"given":"Philippe","family":"Dieud\u00e9","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"},{"name":"Rheumatology Department, Bichat Hospital, AP-HP, 46 Rue H. Huchard, 75018 Paris, France; and"}]},{"given":"Fran\u00e7ois","family":"Corn\u00e9lis","sequence":"additional","affiliation":[{"name":"GenHotel-EA 3886, University Evry-Paris 7 Medical School, Member of the AutoCure European Consortium, CP5727, 91057 Evry-Genopole Cedex, France;"},{"name":"Unit\u00e9 de G\u00e9n\u00e9tique Clinique, P\u00f4le des Laboratoires M\u00e9dicaux-Imagerie-Pharmacie, Lariboisi\u00e8re Hospital, AP-HP, 2 Rue Ambroise Par\u00e9, 75010 Paris, France;"},{"name":"Consultation de G\u00e9n\u00e9tique Adulte, Centre Hospitalier Sud Francilien, 59 Boulevard H. Dunant, 91106 Evry-Corbeil, France"}]},{"name":"European Consortium on Rheumatoid Arthritis Families","sequence":"additional","affiliation":[]}],"member":"341","published-online":{"date-parts":[[2007,1,30]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21575"},{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM197804202981602"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780301102"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(199906)42:6<1071::AID-ANR1>3.0.CO;2-8"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20989"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.21630"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.18.10746"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gene.6364295"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1086\/422827"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1086\/498651"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1323"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/423790"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2006.03.009"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2005.048181"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1038\/ng1673"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.smim.2006.03.008"},{"key":"e_1_3_4_17_2","first-page":"155","volume":"354","author":"Julier C","year":"1991","unstructured":"C Julier, RN Hyer, J Davies, F Merlin, P Soularue, L Briant, G Cathelineau, I Deschamps, JI Rotter, P Froguel, et al. 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