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- Title
The Pro<sup>12</sup>Ala PPARγ gene polymorphism: possible modifier of the activity and severity of thyroid-associated orbitopathy (TAO).
- Authors
Alevizaki, Maria; Mantzou, Emily; Cimponeriu, Adriana; Saltiki, Katerina; Philippou, George; Wiersinga, Wilmar
- Abstract
Objective The PPARγ transcription factor, is involved in both adipogenesis and inflammation, which have been implicated in the pathogenesis of thyroid-associated orbitopathy (TAO). The aim of this study was to explore the possibility that the Pro12Ala polymorphism of the PPARγ gene, associated with a modified transcriptional activity, might be affecting the severity of TAO. Subjects and design We studied two cohorts of patients with Graves’ disease (GD): Group 1 comprised 172 patients of Dutch ethnic origin with TAO, who attended the outpatients’ 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 ( n = 172) and clinical activity score (CAS) ( n = 110), always assessed by the same group of three investigators, were recorded. Autoantibody levels were measured. Results Allele frequency was 11·5%. 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 Pro12Ala carriers (20·1 ± 3·3 vs. 22·1 ± 3·1, P = 0·003, t-test). PPARγ polymorphism carriers had lower TSH-Rab levels (mean rank 61·8 vs. 83·2, P = 0·015) and lower CAS (available in 110 patients) (mean rank 38·9 vs. 55·4, P = 0·022, M– W-test). The frequency of the polymorphism decreased with increasing CAS ( P = 0·023 linear by linear association). Multivariate analysis (step) showed that the association of either proptosis or CAS with the PPARγ gene variant remained significant when age, smoking and TSH-Rab levels were taken into account ( P < 0·01). Conclusions The distribution of the Pro12Ala PPARγ gene polymorphism is equally present in patients with GD with or without TAO. Among patients with TAO this polymorphism is associated with less-severe and less-active disease.
- Subjects
GENETIC polymorphisms; TRANSCRIPTION factors; DIPLOPIA; AUTOANTIBODIES; EXOPHTHALMOS
- Publication
Clinical Endocrinology, 2009, Vol 70, Issue 3, p464
- ISSN
0300-0664
- Publication type
Article
- DOI
10.1111/j.1365-2265.2008.03343.x