A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine

Panicker, Vijay, Cluett, Christie, Shields, Beverley, Murray, Anna, Parnell, Kirstie S., Perry, John R. B., Weedon, Michael N., Singleton, Andrew, Hernandez, Dena, Evans, Jonathan, Durant, Claire, Ferrucci, Luigi, Melzer, David, Saravanan, Ponnusamy, Visser, Theo J., Ceresini, Graziano, Hattersley, Andrew T., Vaidya, Bijay, Dayan, Colin Mark ORCID: https://orcid.org/0000-0002-6557-3462 and Frayling, Timothy M. 2008. A common variation in deiodinase 1 gene DIO1 is associated with the relative levels of free thyroxine and triiodothyronine. Journal of Clinical Endocrinology & Metabolism 93 (8) , pp. 3075-3081. 10.1210/jc.2008-0397

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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 T4 replacement. Suggestive findings were taken forward into three additional studies in people not on T4 (total n = 2513) and metaanalyzed for confirmation. Results: A SNP in the DIO1 gene, rs2235544, was associated with the free T3 to free T4 ratio with genome-wide levels of significance (P = 3.6 × 10−13). The C-allele of this SNP was associated with increased deiodinase 1 (D1) function with resulting increase in free T3/T4 ratio and free T3 and decrease in free T4 and rT3. 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 T3 to free T4. This should prove a valuable tool to assess the relative effects of circulating free T3 vs. free T4 on a wide range of biological parameters.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Subjects:	Q Science > QH Natural history > QH426 Genetics R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher:	The Endocrine Society
ISSN:	0021-972X
Last Modified:	20 Oct 2022 08:44
URI:	https://orca.cardiff.ac.uk/id/eprint/29428

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