{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T09:50:10Z","timestamp":1777542610945,"version":"3.51.4"},"reference-count":36,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,3,27]],"date-time":"2014-03-27T00:00:00Z","timestamp":1395878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Diabetes"],"published-print":{"date-parts":[[2015,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The aim of the study was to investigate the role of the cytotoxic <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u2010lymphocyte\u2010associated protein 4 (<jats:italic><jats:styled-content style=\"fixed-case\">CTLA4<\/jats:styled-content><\/jats:italic>) <jats:styled-content style=\"fixed-case\">G6230A<\/jats:styled-content> variant on the susceptibility of latent autoimmune diabetes in adults (<jats:styled-content style=\"fixed-case\">LADA<\/jats:styled-content>) as a whole and in the subset of patients who share autoimmune thyroid disease (<jats:styled-content style=\"fixed-case\">AITD<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The study included 202 <jats:styled-content style=\"fixed-case\">LADA<\/jats:styled-content>, 1373 patients with early onset type 1 diabetes (<jats:styled-content style=\"fixed-case\">T1D<\/jats:styled-content>), 130 patients with late\u2010onset <jats:styled-content style=\"fixed-case\">T1D<\/jats:styled-content>, 188 patients with non\u2010autoimmune diabetes and 1904 healthy controls. Thyrotropin (thyrotropin\u2010stimulating hormone; <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content>) and antibodies against thyroid peroxidase were analyzed in all patients. The <jats:italic><jats:styled-content style=\"fixed-case\">CTLA4<\/jats:styled-content><\/jats:italic>\u2005<jats:styled-content style=\"fixed-case\">G6230A<\/jats:styled-content> variant was assessed in <jats:styled-content style=\"fixed-case\">LADA<\/jats:styled-content>, early and late\u2010onset <jats:styled-content style=\"fixed-case\">T1D<\/jats:styled-content> patients as well as in the controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The frequency of <jats:italic><jats:styled-content style=\"fixed-case\">CTLA4<\/jats:styled-content><\/jats:italic>\u2005<jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> alleles and genotypes in <jats:styled-content style=\"fixed-case\">LADA<\/jats:styled-content> patients did not differ significantly from that in the other groups, regardless of its association with <jats:styled-content style=\"fixed-case\">AITD<\/jats:styled-content>. We found an increased frequency of <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> allele\u2010containing genotypes within <jats:styled-content style=\"fixed-case\">LADA<\/jats:styled-content> patients who had higher <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content> compared with those with normal <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content> (<jats:italic>P<\/jats:italic> = 0.002). Moreover, <jats:styled-content style=\"fixed-case\">LADA<\/jats:styled-content> patients carrying <jats:styled-content style=\"fixed-case\">G<\/jats:styled-content> allele\u2010containing genotypes were more likely to require insulin therapy within 4 years of diagnosis (<jats:italic>P<\/jats:italic> = 0.002).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">G6230A<\/jats:styled-content>\u2005<jats:italic><jats:styled-content style=\"fixed-case\">CTLA4<\/jats:styled-content><\/jats:italic> variant does not confer susceptibility to <jats:styled-content style=\"fixed-case\">LADA<\/jats:styled-content> in Sardinian patients even when associated with <jats:styled-content style=\"fixed-case\">AITD<\/jats:styled-content>. However, it helps identify a particular subset of <jats:styled-content style=\"fixed-case\">LADA<\/jats:styled-content> patients with more clinically severe disease, both for thyroid dysfunction and diabetes.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1753-0407.12137","type":"journal-article","created":{"date-parts":[[2014,2,17]],"date-time":"2014-02-17T09:58:16Z","timestamp":1392631096000},"page":"68-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Allelic variant in <i><scp>CTLA4<\/scp><\/i> is associated with thyroid failure and faster <i>\u03b2<\/i>\u2010cell exhaustion in latent autoimmune diabetes in adults <i>CTLA4<\/i>\u7b49\u4f4d\u57fa\u56e0\u53d8\u5f02\u4e0e\u6210\u4eba\u8fdf\u53d1\u578b\u81ea\u8eab\u514d\u75ab\u6027\u7cd6\u5c3f\u75c5\u60a3\u8005\u7684\u7532\u72b6\u817a\u529f\u80fd\u8870\u7aed\u4ee5\u53ca<i>\u03b2<\/i>\u2010\u7ec6\u80de\u52a0\u901f\u8870\u7aed\u6709\u5173"],"prefix":"10.1111","volume":"7","author":[{"given":"Alessandro P.","family":"Delitala","sequence":"first","affiliation":[{"name":"Department of Biochemical Science University of Sassari  Sassari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giuseppe","family":"Fanciulli","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine University of Sassari  Sassari Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magdalena","family":"Zoledziewska","sequence":"additional","affiliation":[{"name":"Medical Genetic Unit University of Sassari  Sassari Italy"},{"name":"CNR Institute of Biomedical and Genetic Research  Cagliari 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