. (2008) A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. Journal of Clinical Endocrinology and Metabolism, Volume 93 (Number 8). pp. 3075-3081. ISSN 0021-972X

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Abstract

Introduction: Genetic factors influence circulating thyroid hormone levels, but the common gene variants involved have not been conclusively identified. The genes encoding the iodothyronine deiodinases are good candidates because they alter the balance of thyroid hormones. We aimed to thoroughly examine the role of common variation across the three deiodinase genes in relation to thyroid hormones. Methods: We used HapMap data to select single-nucleotide polymorphisms (SNPs) that captured a large proportion of the common genetic variation across the three deiodinase genes. We analyzed these initially in a cohort of 552 people on T-4 replacement. Suggestive findings were taken forward into three additional studies in people not on T-4 (total n = 2513) and metaanalyzed for confirmation. Results: A SNP in the DIO1 gene, rs2235544, was associated with the free T-3 to free T-4 ratio with genome-wide levels of significance (P = 3.6 x 10(-13)). The C-allele of this SNP was associated with increased deiodinase 1 (D1) function with resulting increase in free T-3/T-4 ratio and free T-3 and decrease in free T-4 and rT(3). There was no effect on serum TSH levels. None of the SNPs in the genes coding for D2 or D3 had any influence on hormone levels. Conclusions: This study provides convincing evidence that common genetic variation in DIO1 alters deiodinase function, resulting in an alteration in the balance of circulating free T-3 to free T-4. This should prove a valuable tool to assess the relative effects of circulating free T-3 vs. free T-4 on a wide range of biological parameters.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH):	Triiodothyronine, Thyroxine, Thyroid gland -- Diseases -- Genetic aspects
Journal or Publication Title:	Journal of Clinical Endocrinology and Metabolism
Publisher:	The Endocrine Society
ISSN:	0021-972X
Date:	August 2008
Volume:	Volume 93
Number:	Number 8
Number of Pages:	7
Page Range:	pp. 3075-3081
Identification Number:	10.1210/jc.2008-0397
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	National Institute on Aging (NIA) , National Institutes of Health (U.S.) (NIH), United States. Department of Health and Human Services, Endocrine Research Fund, South-West National Health Service Research and Development, United Bristol Healthcare NHS Trust
Grant number:	R01 AG24233-01 (NIH)
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URI:	http://wrap.warwick.ac.uk/id/eprint/29578

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