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Cited by 108Thyroid Disorders and TreatmentsGenetic Associations and EpidemiologyThyroid Cancer Diagnosis and Treatment

A new polymorphism in the type II deiodinase gene is associated with circulating thyroid hormone parameters

Peeters, Robin P., van den Beld, Annewieke W., Attalki, Hayat, Toor, Hans van, de Rijke, Yolanda B., Kuiper, George G. J. M., Lamberts, Steven W. J., Janssen, Joop A. M. J. L. +2 more·2005·American Journal of Physiology-Endocrinology and Metabolism
DOI 10.1152/ajpendo.00571.2004
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Abstract

Type II deiodinase (D2) is important in the regulation of local thyroid hormone bioactivity in certain tissues. D2 in skeletal muscle may also play a role in serum triiodothyronine (T(3)) production. In this study, we identified a polymorphism in the 5'-UTR of the D2 gene (D2-ORFa-Gly3Asp). We investigated the association of D2-ORFa-Gly3Asp, and of the previously identified D2-Thr92Ala polymorphism, with serum iodothyronine levels. D2-ORFa-Gly3Asp was identified by sequencing the 5'-UTR of 15 randomly selected individuals. Genotypes for D2-ORFa-Gly3Asp were determined in 156 healthy blood donors (age 46.3 +/- 12.2 yr) and 349 ambulant elderly men (age 77.7 +/- 3.5 yr) and related to serum iodothyronine and TSH levels. D2-ORFa-Asp(3) had an allele frequency of 33.9% in blood bank donors and was associated with serum thyroxine (T(4); Gly/Gly vs. Gly/Asp vs. Asp/Asp = 7.06 +/- 0.14 vs. 6.74 +/- 0.15 vs. 6.29 +/- 0.27 microg/dl, P = 0.01), free T(4) (1.22 +/- 0.02 vs. 1.16 +/- 0.02 vs. 1.06 +/- 0.04 ng/dl, P = 0.001), reverse T(3) (P = 0.01), and T(3)/T(4) ratio (P = 0.002) in a dose-dependent manner, but not with serum T(3) (P = 0.59). In elderly men, D2-ORFa-Asp(3) had a similar frequency but was not associated with serum iodothyronine levels. This new polymorphism in the 5'-UTR of D2 is associated with iodothyronine levels in blood donors but not in elderly men. We hypothesize that this might be explained by the decline in skeletal muscle size during aging, resulting in a rela…

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  • The early observation that particular polymorphisms in DIO2 were dose-dependently associated with free T4 and rT3 could not be replicated.

    “Thus, the early observation that particular polymorphisms in DIO2 were dose-dependently associated with free T4 and rT3 [60] could not be replicated.”

    From 2012 ETA Guidelines: The Use of L-T4 + L-T3 in the Treatment of Hypothyroidism (2012) · cites this paper as [60]

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Authors
Peeters, R. P., van den Beld, A. W., Attalki, H., Toor, H. V., de Rijke, Y. B., Kuiper, G. G. J. M., Lamberts, S. W. J., Janssen, J. A. M. J. L., Uitterlinden, A. G., & Visser, T. J.
Affiliations
Erasmus MC (NL)
ORCID
Venue
American Journal of Physiology-Endocrinology and Metabolism
Publisher
American Physiological Society
Published
2005-07
Volume
289
Issue
1
Pages
E75-E81
ISSN
  • 0193-1849 (ISSN-L)
  • 1522-1555
DOI
10.1152/ajpendo.00571.2004
OpenAlex
W2148290320
Cited by
108
References
6
Citations by year
2025: 3 · 2024: 6 · 2023: 3 · 2022: 5 · 2021: 2 · 2020: 7 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 2 · 2015: 5 · 2014: 7 · 2013: 3 · 2012: 8
FWCI
5.94
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
Funders
ZonMw
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
Keywords
type 2 deiodinase, thyroxine, free thyroxine, reverse T3, T3/T4 ratio, thyroid-stimulating hormone, skeletal muscle, aging, genetic association, gene expression regulation, older men
MeSH terms
Iodothyronine Deiodinase Type II, Aged, Aged, 80 and over, Aging, Aryl Hydrocarbon Hydroxylases, DNA Mutational Analysis, Female, Genetic Testing, Humans, Iodide Peroxidase, Male, Middle Aged, Netherlands, Polymorphism, Genetic, Risk Factors, Statistics as Topic, Thyroid Hormones, Incidence, Age Distribution, Risk Assessment, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide

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