{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T05:02:29Z","timestamp":1783486949192,"version":"3.55.0"},"reference-count":34,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2008,8,20]],"date-time":"2008-08-20T00:00:00Z","timestamp":1219190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2009,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p><jats:bold>Objective\u2002<\/jats:bold> The PPAR\u03b3 transcription factor, is involved in both adipogenesis and inflammation, which have been implicated in the pathogenesis of thyroid\u2010associated orbitopathy (TAO). The aim of this study was to explore the possibility that the Pro<jats:sup>12<\/jats:sup>Ala polymorphism of the PPAR\u03b3 gene, associated with a modified transcriptional activity, might be affecting the severity of TAO.<\/jats:p><jats:p><jats:bold>Subjects and design\u2002\u2002<\/jats:bold> We studied two cohorts of patients with Graves\u2019 disease (GD): Group 1 comprised 172 patients of Dutch ethnic origin with TAO, who attended the outpatients\u2019 clinic, Department of Endocrinology and Orbital Centre of the Academic Medical Centre, Amsterdam. Group 2 comprised 93 consecutive patients with GD of Greek ethnic origin, who did not have TAO. In group 1, exophthalmometry measurements, lid oedema, diplopia (<jats:italic>n<\/jats:italic>\u00a0=\u00a0172) and clinical activity score (CAS) (<jats:italic>n<\/jats:italic>\u00a0=\u00a0110), always assessed by the same group of three investigators, were recorded. Autoantibody levels were measured.<\/jats:p><jats:p><jats:bold>Results\u2002<\/jats:bold> Allele frequency was 11\u00b75%. There was no difference in the distribution of the polymorphism between GD patients with and without TAO. Among group 1 patients proptosis was significantly lower in Pro<jats:sup>12<\/jats:sup>Ala carriers (20\u00b71\u00a0\u00b1\u00a03\u00b73 <jats:italic>vs.<\/jats:italic> 22\u00b71\u00a0\u00b1\u00a03\u00b71, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7003, <jats:italic>t<\/jats:italic>\u2010test). PPAR\u03b3 polymorphism carriers had lower TSH\u2010Rab levels (mean rank 61\u00b78 <jats:italic>vs.<\/jats:italic> 83\u00b72, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7015) and lower CAS (available in 110 patients) (mean rank 38\u00b79 <jats:italic>vs.<\/jats:italic> 55\u00b74, <jats:italic>P<\/jats:italic>\u00a0=\u00a00\u00b7022, M\u2013<jats:italic>W<\/jats:italic>\u2010test). The frequency of the polymorphism decreased with increasing CAS (<jats:italic>P\u00a0=<\/jats:italic>\u00a00\u00b7023 linear by linear association). Multivariate analysis (step) showed that the association of either proptosis or CAS with the PPAR\u03b3 gene variant remained significant when age, smoking and TSH\u2010Rab levels were taken into account (<jats:italic>P\u00a0&lt;<\/jats:italic>\u00a00\u00b701).<\/jats:p><jats:p><jats:bold>Conclusions\u2002<\/jats:bold> The distribution of the Pro<jats:sup>12<\/jats:sup>Ala PPAR\u03b3 gene polymorphism is equally present in patients with GD with or without TAO. Among patients with TAO this polymorphism is associated with less\u2010severe and less\u2010active disease.<\/jats:p>","DOI":"10.1111\/j.1365-2265.2008.03343.x","type":"journal-article","created":{"date-parts":[[2008,8,20]],"date-time":"2008-08-20T10:33:18Z","timestamp":1219228398000},"page":"464-468","source":"Crossref","is-referenced-by-count":11,"title":["The Pro<sup>12<\/sup>Ala PPAR\u03b3 gene polymorphism: possible modifier of the activity and severity of thyroid\u2010associated orbitopathy 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