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Endocrine Abstracts (2015) 37 GP26.09 | DOI: 10.1530/endoabs.37.GP.26.09

University of Groningen, Univ Med Ctr Groningen, Groningen, The Netherlands.


Introduction: The Thr92Ala polymorphism of deiodinase 2 (DIO2) is associated with increased expression in the brain of genes associated with oxidative stress, and may predict favourable response to combination thyroxine (L-T4) plus triiodothyronine (T3) therapy. We examined whether the Thr92Ala polymorphism (rs225014) was associated with differences in thyroid hormone parameters, health-related quality of life (HR-QOL) and cognitive functioning in a large population-based study.

Methods: In 4223 participants from the LifeLines Cohort Study (141 using L-T4) TSH, free thyroxine (FT4), and free T3 (FT3) levels were measured. HR-QOL was assessed with the Short Form-36 questionnaire. The Ruff figural fluency test (RFFT) was used as a sensitive cognitive test. Linear regression with an additive model was used to analyse association between the Thr92Ala genotypes and phenotypes of interest.

Results: Mean (±S.D.) age was 56±10 years and BMI 27.3±4.4 kg/m2 in the L-T4 users vs 51±11 years and 26.4±4.1 kg/m2 in non-L-T4 users; 3847 subjects had normal TSH (0.4–4.5 mU/l), and 90% of L-T4 users were females. The rarer CC genotype (Thr92Ala-D2) of the rs225014 polymorphism in DIO2 was present in 10.2% of the total study population. In non-L-T4 users, the Thr92Ala-D2 polymorphism was not associated with differences in TSH, FT4, FT3, and the FT3/FT4-ratio, and there were no differences in any of the eight HR-QOL domains or the RFFT score. L-T4 users had higher FT4, lower FT3 and lower FT3/FT4-ratio, lower scores on the HR-QOL domains physical functioning, general health and vitality (all P<0.001) and lower RFFT scores (P=0.004). Also, their thyroid hormone parameters, HR-QOL and cognitive functioning were not influenced by the Thr92Ala genotype.

Conclusion: The Thr92Ala polymorphism of DIO2 was not associated with thyroid parameters, HR-QOL and cognitive functioning in the general population and subjects with hypothyroidism.

Disclosure: This work was supported by NCHA, Netherlands Consortium for Healthy Ageing, Bio-SHaRE-EU, Biobank Standardisation and Harmonisation for research excellence in the European Union. Bioresource research impact factor BRIF4568.

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