The association of polymorphisms in the type 1 and 2 deiodinase genes with circulating thyroid hormone parameters and atrophy of the medial temporal lobe.
BACKGROUND
Thyroid function has been related to Alzheimer disease (AD) and neuroimaging 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 in 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 neuroimaging markers of AD.


METHODS
The Rotterdam Scan Study is a population-based cohort study among 1,077 elderly individuals aged 60-90 yr.


METHODS
DIO1 and DIO2 polymorphisms and serum TSH, free T4, T3, and reverse T3 (rT3) levels were determined in 995 nondemented elderly, including 473 persons with assessments of hippocampal and amygdalar volume on brain magnetic resonance imaging.


RESULTS
Carriers of the D1a-T allele had higher serum free T4 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.


CONCLUSIONS
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 magnetic resonance imaging markers of AD. This suggests that the previously reported association between iodothyronine levels and brain atrophy reflects comorbidity or nonthyroidal illness rather than thyroid hormones being involved in developing AD.
de Jong
Frank Jan
FJ
Department of Epidemiology, Biostatistics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
Peeters
Robin P
RP
den Heijer
Tom
T
van der Deure
Wendy M
WM
Hofman
Albert
A
Uitterlinden
André G
AG
Visser
Theo J
TJ
Breteler
Monique M B
MM
D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000235:genetics; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D000679:Amygdala / Q000473:pathology; D001284:Atrophy; D042241:Early Diagnosis; D005260:Female; D008040:Genetic Linkage; D005819:Genetic Markers; D006624:Hippocampus / Q000473:pathology; D006801:Humans; D007453:Iodide Peroxidase / Q000235:genetics*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D013702:Temporal Lobe / Q000473:pathology*; D013959:Thyroid Diseases / Q000235:genetics* / Q000473:pathology; D013974:Thyroxine / Q000097:blood*; D014284:Triiodothyronine / Q000097:blood*; D000097564:Iodothyronine Deiodinase Type II
D005819:Genetic Markers; D007453:Iodide Peroxidase; D013974:Thyroxine; D014284:Triiodothyronine; D000097564:Iodothyronine Deiodinase Type II