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This version published online on November 14, 2006
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2006-1331
A more recent version of this article appeared on February 1, 2007
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Submitted on June 21, 2006
Accepted on November 3, 2006

The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe

Frank Jan de Jong, Robin P. Peeters, Tom den Heijer, Wendy M. van der Deure, Albert Hofman, André G. Uitterlinden, Theo J. Visser, and Monique M.B. Breteler*

Departments of Epidemiology & Biostatistics,Neurology,Internal Medicine,and Clinical Chemistry,Erasmus Medical Center, Rotterdam, The Netherlands

* To whom correspondence should be addressed. E-mail: m.breteler{at}erasmusmc.nl.

Context: Thyroid function has been related to Alzheimer disease (AD) and neuro-imaging markers thereof. Whether thyroid dysfunction contributes to or results from developing AD remains unclear. Variations in the deiodinase type 1 (DIO1) and type 2 (DIO2) genes that potentially alter thyroid hormone bioactivity may help elucidating the role of thyroid function in AD.

Objective: We investigated the association of recently identified polymorphisms in the DIO1 (D1a-C/T, D1b-A/G) and DIO2 (D2-ORFa-Gly3Asp, D2-Thr92Ala) genes with circulating thyroid parameters, and early neuro-imaging markers of AD.

Design and participants: The Rotterdam Scan Study, a population-based cohort study among 1,077 elderly individuals aged 60-90 yr.

Main outcome measures: DIO1 and DIO2 polymorphisms and serum TSH, fT4, T3 and rT3 levels were determined in 995 non-demented elderly, including 473 persons with assessments of hippocampal and amygdalar volume on brain magnetic resonance imaging (MRI).

Results: Carriers of the D1a-T allele had higher serum fT4 and rT3, lower T3 and lower T3/rT3. The D1b-G allele was associated with higher serum T3 and T3/rT3. The DIO2 variants were not associated with serum thyroid parameters. No associations were found with hippocampal or amygdalar volume.

Conclusion: This is the first study to report an association of D1a-C/T and D1b-A/G polymorphisms with iodothyronine levels in the elderly. Polymorphisms in the DIO1 and DIO2 genes are not associated with early MRI markers of AD. This suggests that the previously reported association between iodothyronine levels and brain atrophy reflects comorbidity or non-thyroidal illness rather than thyroid hormones being involved in developing AD.
Key words: thyroid hormone metabolism • D1 • D2 • brain • aging




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