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 0021-972x

Full text not available from this repository.

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
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Journal of Clinical Endocrinology & Metabolism
Publisher:	Endocrine Society
ISSN:	0021-972x
Date:	May 2009
Volume:	Vol.94
Number:	No.5
Number of Pages:	7
Page Range:	pp. 1623-1629
Identification Number:	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
URI:	http://wrap.warwick.ac.uk/id/eprint/27979

Data sourced from Thomson Reuters' Web of Knowledge

Request changes to a record

Actions (login required)

View Item