Polymorphisms in the brain-specific thyroid hormone transporter OATP1C1 are associated with fatigue and depression in hypothyroid patients

Wendy Deure, BC Appelhof, Robin Peeters, WM Wiersinga, EM Wekking, J Huyser, AH Schene, Kedir Adal, WJG Hoogendijk, Theo Visser, E Fliers

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Abstract

Introduction Some hypothyroid patients continue to have significant impairments in psychological well-being, despite adequate treatment with levothyroxine (LT4). T4 transport across the blood-brain barrier is one of the crucial processes for thyroid hormone action in the brain. OATP1C1, a thyroid hormone transporter expressed at the blood-brain barrier, is considered to play a key role in delivering serum T4 to the brain. Objective To examine whether polymorphisms in OATP1C1 are determinants of well-being, neurocognitive functioning and preference for replacement therapy with a combination of LT4 and liothyronine (LT3). Design and participants We studied 141 patients with primary autoimmune hypothyroidism, adequately treated with LT4 monotherapy and participating in a randomized clinical trial comparing LT4 therapy with LT4-LT3 combination therapy. Outcome measurements Different questionnaires on well-being and neurocognitive tests were performed at baseline. Serum thyroid parameters, OATP1C1-intron3C > T, OATP1C1-Pro143Thr and OATP1C1-C3035T polymorphisms were determined. Results Allele frequencies of the OATP1C1 polymorphisms in patients with primary hypothyroidism were similar to those of healthy controls. Both the OATP1C1-intron3C > T and the OATP1C1-C3035T polymorphism, but not the OATP1C1-Pro143Thr polymorphism, were associated with symptoms of fatigue and depression. OATP1C1 polymorphisms were not associated with measures of neurocognitive functioning or preference for combined LT4-LT3 therapy. Conclusions OATP1C1 polymorphisms are associated with fatigue and depression, but do not explain differences in neurocognitive functioning or appreciation of LT4-LT3 combination therapy. Future studies are needed to confirm these findings.
Original languageUndefined/Unknown
Pages (from-to)804-811
Number of pages8
JournalClinical Endocrinology
Volume69
Issue number5
DOIs
Publication statusPublished - 2008

Research programs

  • EMC MM-01-39-03

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