{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T14:41:59Z","timestamp":1761662519255},"reference-count":26,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2007,7,3]],"date-time":"2007-07-03T00:00:00Z","timestamp":1183420800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2007,7,3]],"date-time":"2007-07-03T00:00:00Z","timestamp":1183420800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Arthritis Res Ther"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The integrin \u03b1v\u03b23, whose \u03b1v subunit is encoded by the <jats:italic>ITGAV<\/jats:italic> gene, plays a key role in angiogenesis. Hyperangiogenesis is involved in rheumatoid arthritis (RA) and the <jats:italic>ITGAV<\/jats:italic> gene is located in 2q31, one of the suggested RA susceptibility loci. Our aim was to test the <jats:italic>ITGAV<\/jats:italic> gene for association and linkage to RA in a family-based study from the European Caucasian population.<\/jats:p><jats:p>Two single nucleotide polymorphisms were genotyped by PCR-restriction fragment length polymorphism in 100 French Caucasian RA trio families (one RA patient and both parents), 100 other French families and 265 European families available for replication. The genetic analyses for association and linkage were performed using the comparison of allelic frequencies (affected family-based controls), the transmission disequilibrium test, and the genotype relative risk.<\/jats:p><jats:p>We observed a significant RA association for the C allele of rs3738919 in the first sample (affected family-based controls, RA index cases 66.5% versus controls 56.7%; <jats:italic>P =<\/jats:italic> 0.04). The second sample showed the same trend, and the third sample again showed a significant RA association. When all sets were combined, the association was confirmed (affected family-based controls, RA index cases 64.6% versus controls 58.1%; <jats:italic>P =<\/jats:italic> 0.005). The rs3738919-C allele was also linked to RA (transmission disequilibrium test, 56.5% versus50% of transmission; <jats:italic>P =<\/jats:italic> 0.009) and the C-allele-containing genotype was more frequent in RA index cases than in controls (RA index cases 372 versus controls 339; <jats:italic>P =<\/jats:italic> 0.002, odds ratio = 1.94, 95% confidence interval = 1.3\u20132.9).<\/jats:p><jats:p>The rs3738919-C allele of the <jats:italic>ITGAV<\/jats:italic> gene is associated with RA in the European Caucasian population, suggesting <jats:italic>ITGAV<\/jats:italic> as a new minor RA susceptibility gene.<\/jats:p>","DOI":"10.1186\/ar2221","type":"journal-article","created":{"date-parts":[[2007,7,5]],"date-time":"2007-07-05T18:13:03Z","timestamp":1183659183000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The ITGAVrs3738919-C allele is associated with rheumatoid arthritis in the European Caucasian population: a family-based study"],"prefix":"10.1186","volume":"9","author":[{"given":"Laurent","family":"Jacq","sequence":"first","affiliation":[]},{"given":"Sophie","family":"Garnier","sequence":"additional","affiliation":[]},{"given":"Philippe","family":"Dieud\u00e9","sequence":"additional","affiliation":[]},{"given":"La\u00ebtitia","family":"Michou","sequence":"additional","affiliation":[]},{"given":"C\u00e9line","family":"Pierlot","sequence":"additional","affiliation":[]},{"given":"Paola","family":"Migliorini","sequence":"additional","affiliation":[]},{"given":"Alejandro","family":"Balsa","sequence":"additional","affiliation":[]},{"given":"Ren\u00e9","family":"Westhovens","sequence":"additional","affiliation":[]},{"given":"Pilar","family":"Barrera","sequence":"additional","affiliation":[]},{"given":"Helena","family":"Alves","sequence":"additional","affiliation":[]},{"given":"Carlos","family":"Vaz","sequence":"additional","affiliation":[]},{"given":"Manuela","family":"Fernandes","sequence":"additional","affiliation":[]},{"given":"Dora","family":"Pascual-Salcedo","sequence":"additional","affiliation":[]},{"given":"Stefano","family":"Bombardieri","sequence":"additional","affiliation":[]},{"given":"Jan","family":"Dequeker","sequence":"additional","affiliation":[]},{"given":"Timothy R","family":"Radstake","sequence":"additional","affiliation":[]},{"given":"Piet","family":"Van Riel","sequence":"additional","affiliation":[]},{"given":"Leo","family":"van de Putte","sequence":"additional","affiliation":[]},{"given":"Antonio","family":"Lopes-Vaz","sequence":"additional","affiliation":[]},{"given":"Elodie","family":"Glikmans","sequence":"additional","affiliation":[]},{"given":"Sandra","family":"Barbet","sequence":"additional","affiliation":[]},{"given":"Sandra","family":"Lasbleiz","sequence":"additional","affiliation":[]},{"given":"Isabelle","family":"Lemaire","sequence":"additional","affiliation":[]},{"given":"Patrick","family":"Quillet","sequence":"additional","affiliation":[]},{"given":"Pascal","family":"Hilliquin","sequence":"additional","affiliation":[]},{"given":"Vitor Hugo","family":"Teixeira","sequence":"additional","affiliation":[]},{"given":"Elisabeth","family":"Petit-Teixeira","sequence":"additional","affiliation":[]},{"given":"Hamdi","family":"Mbarek","sequence":"additional","affiliation":[]},{"given":"Bernard","family":"Prum","sequence":"additional","affiliation":[]},{"given":"Thomas","family":"Bardin","sequence":"additional","affiliation":[]},{"given":"Fran\u00e7ois","family":"Corn\u00e9lis","sequence":"additional","affiliation":[]},{"name":"the European Consortium on Rheumatoid Arthritis Families","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2007,7,3]]},"reference":[{"key":"2072_CR1","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1002\/1529-0131(199906)42:6<1071::AID-ANR1>3.0.CO;2-8","volume":"42","author":"MF Seldin","year":"1999","unstructured":"Seldin MF, Amos CI, Ward R, Gregersen PK: The genetics revolution and the assault on rheumatoid arthritis. Arthritis Rheum. 1999, 42: 1071-1079. 10.1002\/1529-0131(199906)42:6<1071::AID-ANR1>3.0.CO;2-8.","journal-title":"Arthritis Rheum"},{"key":"2072_CR2","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/S0092-8674(00)81109-5","volume":"85","author":"M Feldmann","year":"1996","unstructured":"Feldmann M, Brennan FM, Maini RN: Rheumatoid arthritis. Cell. 1996, 85: 307-331. 10.1016\/S0092-8674(00)81109-5.","journal-title":"Cell"},{"key":"2072_CR3","doi-asserted-by":"publisher","first-page":"R1200","DOI":"10.1186\/ar1812","volume":"7","author":"P Dieud\u00e9","year":"2005","unstructured":"Dieud\u00e9 P, Garnier S, Michou L, Petit-Teixeira E, Glikmans E, Pierlot C, Lasbleiz S, Bardin T, Prum B, Cornelis F: Rheumatoid arthritis seropositive for the rheumatoid factor is linked to the protein tyrosine phosphatase nonreceptor 22-620W allele. Arthritis Res Ther. 2005, 7: R1200-R1207. 10.1186\/ar1812.","journal-title":"Arthritis Res Ther"},{"key":"2072_CR4","doi-asserted-by":"publisher","first-page":"R79","DOI":"10.1186\/ar1949","volume":"8","author":"L Michou","year":"2006","unstructured":"Michou L, Croiseau P, Petit-Teixeira E, du Montcel ST, Lemaire I, Pierlot C, Osorio J, Frigui W, Lasbleiz S, Quillet P, et al: Validation of the reshaped shared epitope HLA-DRB1 classification in rheumatoid arthritis. Arthritis Res Ther. 2006, 8: R79-10.1186\/ar1949.","journal-title":"Arthritis Res Ther"},{"key":"2072_CR5","doi-asserted-by":"publisher","first-page":"2757","DOI":"10.1002\/art.20458","volume":"50","author":"Y Osorio","year":"2004","unstructured":"Osorio Y, Fortea J, Bukulmez H, Petit-Teixeira E, Michou L, Pierlot C, Cailleau-Moindrault S, Lemaire I, Lasbleiz S, Alibert O, et al: Dense genome-wide linkage analysis of rheumatoid arthritis including covariates. Arthritis Rheum. 2004, 50: 2757-2765. 10.1002\/art.20458.","journal-title":"Arthritis Rheum"},{"key":"2072_CR6","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1172\/JCI6869","volume":"103","author":"BP Eliceiri","year":"1999","unstructured":"Eliceiri BP, Cherech DA: The role of alphav integrins during angiogenesis: insights into potential mechanisms of action and clinical developments. J Clin Invest. 1999, 103: 1227-1230.","journal-title":"J Clin Invest"},{"key":"2072_CR7","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1126\/science.270.5241.1500","volume":"270","author":"M Friedlander","year":"1995","unstructured":"Friedlander M, Brooks PC, Shaffer RW, Kincaid CM, Varner JA, Cheresh DA: Definition of two angiogenic pathways by distinct alpha v integrins. Science. 1995, 270: 1500-1502. 10.1126\/science.270.5241.1500.","journal-title":"Science"},{"key":"2072_CR8","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/S0092-8674(00)81618-9","volume":"95","author":"BL Bader","year":"1998","unstructured":"Bader BL, Rayburn H, Crowley D, Hynes RO: Extensive vasculogenesis, angiogenesis, and organogenesis precede lethality in mice lacking all alpha v integrins. Cell. 1998, 95: 507-519. 10.1016\/S0092-8674(00)81618-9.","journal-title":"Cell"},{"key":"2072_CR9","doi-asserted-by":"publisher","first-page":"2055","DOI":"10.1002\/1529-0131(200109)44:9<2055::AID-ART355>3.0.CO;2-2","volume":"44","author":"S Ballara","year":"2001","unstructured":"Ballara S, Taylor PC, Reusch P, Marm\u00e9 D, Feldmann M, Maini RN, Paleolog EM: Raised serum vascular endothelial growth factor levels are associated with destructive change in inflammatory arthritis. Arthritis Rheum. 2001, 44: 2055-2064. 10.1002\/1529-0131(200109)44:9<2055::AID-ART355>3.0.CO;2-2.","journal-title":"Arthritis Rheum"},{"key":"2072_CR10","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/S0140-6736(89)91305-6","volume":"1","author":"DR Blake","year":"1989","unstructured":"Blake DR, Merry P, Unsworth J, Kidd BL, Outhwaite JM, Ballard R, Morris CJ, Gray L, Lunec J: Hypoxic-reperfusion injury in the inflamed human joint. Lancet. 1989, 1: 289-293. 10.1016\/S0140-6736(89)91305-6.","journal-title":"Lancet"},{"key":"2072_CR11","doi-asserted-by":"publisher","first-page":"2056","DOI":"10.1002\/1529-0131(200009)43:9<2056::AID-ANR17>3.0.CO;2-2","volume":"43","author":"M de Bandt","year":"2000","unstructured":"de Bandt M, Grossin M, Weber AJ, Chopin M, Elbim C, Pla M, Gougerot-Pocidalo MA, Gaudry M: Suppression of arthritis and protection from bone destruction by treatment with TNP-470\/AGM-1470 in a transgenic mouse model of rheumatoid arthritis. Arthritis Rheum. 2000, 43: 2056-2063. 10.1002\/1529-0131(200009)43:9<2056::AID-ANR17>3.0.CO;2-2.","journal-title":"Arthritis Rheum"},{"key":"2072_CR12","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1172\/JCI3756","volume":"103","author":"CM Storgard","year":"1999","unstructured":"Storgard CM, Stupack DG, Jonczyk A, Goodman SL, Fox RI, Cheresh DA: Decreased angiogenesis and arthritic disease in rabbits treated with an alphavbeta3 antagonist. J Clin Invest. 1999, 103: 47-54.","journal-title":"J Clin Invest"},{"key":"2072_CR13","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1186\/ar327","volume":"3","author":"DM Gerlag","year":"2001","unstructured":"Gerlag DM, Borges E, Tak PP, Ellerby HM, Bredesen DE, Pasqualini R: Suppression of murine collagen-induced arthritis by targeted apoptosis of synovial neovasculature. Arthritis Res. 2001, 3: 357-361. 10.1186\/ar327.","journal-title":"Arthritis Res"},{"key":"2072_CR14","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1002\/1529-0131(200101)44:1<128::AID-ANR17>3.0.CO;2-M","volume":"44","author":"AM Badger","year":"3005","unstructured":"Badger AM, Blake S, Kapadia R, Sarkar S, Levin J, Swift BA, Hoffman SJ, Stroup GB, Miller WH, Gowen M, et al: Disease-modifying activity of SB 27 an orally active, nonpeptide alphavbeta3 (vitronectin receptor) antagonist, in rat adjuvant-induced arthritis. Arthritis Rheum. 3005, 44: 128-137. 10.1002\/1529-0131(200101)44:1<128::AID-ANR17>3.0.CO;2-M.","journal-title":"Arthritis Rheum"},{"key":"2072_CR15","doi-asserted-by":"publisher","first-page":"ii96","DOI":"10.1136\/ard.61.suppl_2.ii96","volume":"61","author":"RL Wilder","year":"2002","unstructured":"Wilder RL: Integrin alpha V beta 3 as a target for treatment of rheumatoid arthritis and related rheumatic diseases. Ann Rheum Dis. 2002, 61: ii96-ii99.","journal-title":"Ann Rheum Dis"},{"key":"2072_CR16","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1002\/art.1780310302","volume":"31","author":"FC Arnett","year":"1988","unstructured":"Arnett FC, Edworthy SM, Bloch DA: The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988, 31: 315-324. 10.1002\/art.1780310302.","journal-title":"Arthritis Rheum"},{"key":"2072_CR17","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1002\/art.1780301102","volume":"30","author":"PK Gregersen","year":"1987","unstructured":"Gregersen PK, Silver J, Winchester RJ: The shared epitope hypothesis. An approach to understanding the molecular genetics of susceptibility to rheumatoid arthritis. Arthritis Rheum. 1987, 30: 1205-1213. 10.1002\/art.1780301102.","journal-title":"Arthritis Rheum"},{"key":"2072_CR18","volume-title":"A Laboratory Manual","author":"P Sambrook","year":"1989","unstructured":"Sambrook P, Fritsch E, Maniatis T: A Laboratory Manual. 1989, New York: Cold Spring Harbor Laboratory Press, 1: 2","edition":"2"},{"key":"2072_CR19","unstructured":"National Center for Biotechnology Information. [http:\/\/www.ncbi.nlm.nih.gov\/]"},{"key":"2072_CR20","unstructured":"The Bio-web. [http:\/\/www.cellbiol.com\/soft.htm]"},{"key":"2072_CR21","first-page":"314","volume":"32","author":"D Botstein","year":"1980","unstructured":"Botstein D, White RL, Skolnick M, Davis RW: Construction of a genetic linkage map in man using restriction fragment length polymorphisms. Am J Hum Genet. 1980, 32: 314-331.","journal-title":"Am J Hum Genet"},{"key":"2072_CR22","unstructured":"Genhotel EA-3886. [http:\/\/www.genhotel.com\/]"},{"key":"2072_CR23","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1136\/ard.2006.061390","volume":"66","author":"S Garnier","year":"2007","unstructured":"Garnier S, Dieud\u00e9 P, Michou L, Barbet S, Tan A, Lasbleiz S, Bardin T, Prum B, Cornelis F: IRF5 rs2004640-T allele, the new genetic factor for systemic lupus erythematosus, is not associated with rheumatoid arthritis. Ann Rheum Dis. 2007, 66: 828-831. 10.1136\/ard.2006.061390.","journal-title":"Ann Rheum Dis"},{"key":"2072_CR24","first-page":"506","volume":"52","author":"RS Spielman","year":"1993","unstructured":"Spielman RS, McGinnis RE, Ewens WJ: Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). Am J Hum Genet. 1993, 52: 506-516.","journal-title":"Am J Hum Genet"},{"key":"2072_CR25","first-page":"487","volume":"57","author":"G Thomson","year":"1995","unstructured":"Thomson G: Mapping disease genes: family-based association studies. Am J Hum Genet. 1995, 57: 487-498.","journal-title":"Am J Hum Genet"},{"key":"2072_CR26","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1111\/j.1399-0039.1983.tb01183.x","volume":"22","author":"GM Lathrop","year":"1983","unstructured":"Lathrop GM: Estimating genotype relative risks. Tissue Antigens. 1983, 22: 160-162.","journal-title":"Tissue Antigens"}],"container-title":["Arthritis Research &amp; Therapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar2221.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/ar2221\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/ar2221.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,8]],"date-time":"2024-10-08T10:32:29Z","timestamp":1728383549000},"score":1,"resource":{"primary":{"URL":"https:\/\/arthritis-research.biomedcentral.com\/articles\/10.1186\/ar2221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2007,7,3]]},"references-count":26,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2007,8]]}},"alternative-id":["2072"],"URL":"https:\/\/doi.org\/10.1186\/ar2221","relation":{},"ISSN":["1478-6354"],"issn-type":[{"type":"electronic","value":"1478-6354"}],"subject":[],"published":{"date-parts":[[2007,7,3]]},"assertion":[{"value":"22 February 2007","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 May 2007","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2007","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 July 2007","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}}],"article-number":"R63"}}