Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients
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. ISSN 0021-972xFull text not available from this repository.
Official URL: http://dx.doi.org/10.1210/jc.2008-1301
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|
|Subjects:||R Medicine > RC Internal medicine|
|Divisions:||Faculty of Medicine > Warwick Medical School|
|Journal or Publication Title:||Journal of Clinical Endocrinology & Metabolism|
|Official Date:||May 2009|
|Number of Pages:||7|
|Page Range:||pp. 1623-1629|
|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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