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Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients
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Panicker, Vijay, Saravanan, Ponnusamy, Vaidya, Bijay, Evans, Jonathan, Hattersley, Andrew T., Frayling, Timothy M. and Dayan, Colin M. (2009) Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients. Journal of Clinical Endocrinology & Metabolism, Vol.94 (No.5). pp. 1623-1629. doi:10.1210/jc.2008-1301 ISSN 0021-972x.
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Official URL: http://dx.doi.org/10.1210/jc.2008-1301
Abstract
Introduction: Animal studies suggest that up to 80% of intracellular T-3 in the brain is derived from circulating T-4 by local deiodination. We hypothesized that in patients on T-4 common variants in the deiodinase genes might influence baseline psychological well-being and any improvement on combined T-4/T-3 without necessarily affecting serum thyroid hormone levels.
Methods: We analyzed common variants in the three deiodinase genes vs. baseline psychological morbidity and response to T-4/T-3 in 552 subjects on T-4 from the Weston Area T-4 T-3 Study (WATTS). Primary outcome was improvement in psychological well-being assessed by the General Health Questionnaire 12 (GHQ-12).
Results: The rarer CC genotype of the rs225014 polymorphism in the deiodinase 2 gene (DIO2) was present in 16% of the study population and was associated with worse baseline GHQ scores in patients on T-4 (CC vs. TT genotype: 14.1 vs. 12.8, P = 0.03). In addition, this genotype showed greater improvement on T-4/T-3 therapy compared with T-4 only by 2.3 GHQ points at 3 months and 1.4 at 12 months (P = 0.03 for repeated measures ANOVA). This polymorphism had no impact on circulating thyroid hormone levels.
Conclusions: Our results require replication but suggest that commonly inherited variation in the DIO2 gene is associated both with impaired baseline psychological well-being on T-4 and enhanced response to combination T-4/T-3 therapy, but did not affect serum thyroid hormone levels. (J Clin Endocrinol Metab 94: 1623-1629, 2009)
Item Type: | Journal Article | ||||
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Subjects: | R Medicine > RC Internal medicine | ||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | ||||
Journal or Publication Title: | Journal of Clinical Endocrinology & Metabolism | ||||
Publisher: | Endocrine Society | ||||
ISSN: | 0021-972x | ||||
Official Date: | May 2009 | ||||
Dates: |
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Volume: | Vol.94 | ||||
Number: | No.5 | ||||
Number of Pages: | 7 | ||||
Page Range: | pp. 1623-1629 | ||||
DOI: | 10.1210/jc.2008-1301 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Funder: | South West National Health Service Research and Development, Goldshield Pharmaceuticals PLC, Athelstan & Amy Saw Medical Research Fellowship through the Faculty of Medicine, Dentistry and Health Sciences at the University of Western Australia |
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