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


METHODS
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.


METHODS
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.
van der Deure
Wendy M
WM
Department of Internal Medicine, Erasmus University Medical Center Rotterdam, The Netherlands.
Appelhof
Bente C
BC
Peeters
Robin P
RP
Wiersinga
Wilmar M
WM
Wekking
Ellie M
EM
Huyser
Jochanan
J
Schene
Aart H
AH
Tijssen
Jan G P
JG
Hoogendijk
Witte J G
WJ
Visser
Theo J
TJ
Fliers
Eric
E
D000293:Adolescent; D000328:Adult; D000368:Aged; D001921:Brain / Q000378:metabolism*; D003071:Cognition / Q000502:physiology; D003863:Depression / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D005221:Fatigue / Q000150:complications / Q000235:genetics* / Q000378:metabolism; D008040:Genetic Linkage; D020249:Hormone Replacement Therapy; D006801:Humans; D007037:Hypothyroidism / Q000150:complications / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D009928:Organ Specificity / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D016032:Randomized Controlled Trials as Topic; D013963:Thyroid Hormones / Q000008:administration & dosage / Q000378:metabolism; D055815:Young Adult
D027361:Organic Anion Transporters; C473187:SLCO1C1 protein, human; D013963:Thyroid Hormones