{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T01:26:41Z","timestamp":1791163601647,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2006,7,25]],"date-time":"2006-07-25T00:00:00Z","timestamp":1153785600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Arthritis &amp; Rheumatism"],"published-print":{"date-parts":[[2006,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Cytotoxic T lymphocyte\u2013associated antigen 4 (CTLA\u20104) is a key negative regulator of the T cell immune response, and the <jats:italic>CTLA4<\/jats:italic> gene is highly polymorphic. Many positive associations between <jats:italic>CTLA4<\/jats:italic> single\u2010nucleotide polymorphisms (SNPs) and various autoimmune diseases have been identified. Two <jats:italic>CTLA4<\/jats:italic> SNPs that are important relative to genetic susceptibility in human autoimmune diseases are the +49GA polymorphism in exon 1 and the CT60A\/G polymorphism in the 3\u2032\u2010untranslated region. Using these 2 polymorphisms as markers, we investigated possible genetic associations of <jats:italic>CTLA4<\/jats:italic> in Australian patients with primary Sj\u00f6gren's syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>One hundred eleven Australian Caucasian patients with primary SS and 156 population\u2010based controls were genotyped for <jats:italic>CTLA4<\/jats:italic> by polymerase chain reaction\u2013restriction fragment length polymorphism methods, using the restriction enzymes <jats:italic>Bse<\/jats:italic>XI (+49G\/A) and <jats:italic>HpyCh4<\/jats:italic> IV (CT60).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The CT60 and +49G\/A SNPs were in strong linkage disequilibrium, and only 3 haplotypes were observed. Significant differences in the haplotype frequencies between patients with primary SS and controls (<jats:italic>P<\/jats:italic> = 0.032) were observed, with susceptibility to primary SS associated with both the +49A;CT60A haplotype and the +49A;CT60G haplotype, whereas the +49G;CT60G haplotype was protective against primary SS. The +49A;CT60G haplotype association was predominantly with Ro\/La autoantibody\u2013positive primary SS, and the dose of this haplotype influenced the severity of daytime sleepiness (<jats:italic>P<\/jats:italic> = 0.036). The +49A;CT60A haplotype appeared to be protective against the development of Raynaud's phenomenon in patients with primary SS (odds ratio 0.49, 95% confidence interval 0.27\u20130.91).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The <jats:italic>CTLA4<\/jats:italic> +49G\/A and CT60 haplotypes are associated with susceptibility to primary SS and with some extraglandular manifestations of the disease.<\/jats:p><\/jats:sec>","DOI":"10.1002\/art.22004","type":"journal-article","created":{"date-parts":[[2006,7,25]],"date-time":"2006-07-25T23:46:56Z","timestamp":1153871216000},"page":"2434-2440","source":"Crossref","is-referenced-by-count":53,"title":["Influence of <i>CTLA4<\/i> haplotypes on susceptibility and some extraglandular manifestations in primary Sj\u00f6gren's syndrome"],"prefix":"10.1002","volume":"54","author":[{"given":"Sarah","family":"Downie\u2010Doyle","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noushin","family":"Bayat","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen","family":"Rischmueller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Lester","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,7,25]]},"reference":[{"key":"e_1_2_5_2_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.5673"},{"key":"e_1_2_5_3_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar1158"},{"key":"e_1_2_5_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature01621"},{"key":"e_1_2_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0198-8859(03)00171-X"},{"key":"e_1_2_5_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201214"},{"key":"e_1_2_5_7_2","doi-asserted-by":"publisher","DOI":"10.1034\/j.1399-0039.2001.580110.x"},{"key":"e_1_2_5_8_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201423"},{"key":"e_1_2_5_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/ar599"},{"key":"e_1_2_5_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2249.1998.00504.x"},{"key":"e_1_2_5_11_2","doi-asserted-by":"publisher","DOI":"10.1136\/ard.61.6.554"},{"key":"e_1_2_5_12_2","first-page":"2406","article-title":"Increased severity of lower urinary tract symptoms and daytime somnolence in primary Sjogren's syndrome","volume":"30","author":"Walker J","year":"2003","journal-title":"J Rheumatol"},{"key":"e_1_2_5_13_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20347"},{"key":"e_1_2_5_14_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.2004.00312.x"},{"key":"e_1_2_5_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2004.03.050"},{"key":"e_1_2_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/sleep\/14.6.540"},{"key":"e_1_2_5_17_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2370.2003.00430.x"},{"key":"e_1_2_5_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20093"},{"key":"e_1_2_5_19_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.164.21.2387-b"},{"key":"e_1_2_5_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.10221"},{"key":"e_1_2_5_21_2","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.20045"},{"key":"e_1_2_5_22_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.155.4.1776"},{"key":"e_1_2_5_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.20997"},{"key":"e_1_2_5_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1167"},{"key":"e_1_2_5_25_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206894200"},{"key":"e_1_2_5_26_2","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.165.11.6606"},{"key":"e_1_2_5_27_2","doi-asserted-by":"publisher","DOI":"10.1186\/1740-2557-2-8"},{"key":"e_1_2_5_28_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.12.4.673"},{"key":"e_1_2_5_29_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.19.1.565"},{"key":"e_1_2_5_30_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/41.10.1206"},{"key":"e_1_2_5_31_2","doi-asserted-by":"publisher","DOI":"10.1002\/1529-0131(200007)43:7<1647::AID-ANR31>3.0.CO;2-P"},{"key":"e_1_2_5_32_2","doi-asserted-by":"publisher","DOI":"10.1097\/00004650-200303000-00002"}],"container-title":["Arthritis &amp; 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