Common variation in the DIO2 gene predicts baseline psychological well-being and response to combination thyroxine plus triiodothyronine therapy in hypothyroid patients.
BACKGROUND
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.
Panicker
Vijay
V
Henry Wellcome Laboratories for Integrative Neurosciences and Endocrinology, University of Bristol, Dorothy Hodgkin Building, Whitson Street, Bristol BS1 3NY, United Kingdom.
Saravanan
Ponnusamy
P
Vaidya
Bijay
B
Evans
Jonathan
J
Hattersley
Andrew T
AT
Frayling
Timothy M
TM
Dayan
Colin M
CM
D000328:Adult; D004247:DNA / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006304:Health Status; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000188:drug therapy / Q000235:genetics* / Q000523:psychology*; D007453:Iodide Peroxidase / Q000235:genetics*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D011594:Psychometrics; D011795:Surveys and Questionnaires; D013960:Thyroid Function Tests; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood / Q000627:therapeutic use*; D014284:Triiodothyronine / Q000097:blood / Q000627:therapeutic use*; D000097564:Iodothyronine Deiodinase Type II
D004247:DNA; D007453:Iodide Peroxidase; D013972:Thyrotropin; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II