DNA methylation at a nutritionally sensitive region of the PAX8 gene is associated with thyroid volume and function in Gambian children

Candler, Toby, Kessler, Noah J., Gunasekara, Chathura J., Ward, Kate A., James, Philip, Laritsky, Eleonora, Baker, Maria S., Dyer, Roger, Elango, Rajavel, Jeffries, David, Waterland, Robert A., Moore, Sophie E., Ludgate, Marian, Prentice, Andrew M. and Silver, Matt J. 2021. DNA methylation at a nutritionally sensitive region of the PAX8 gene is associated with thyroid volume and function in Gambian children. Science Advances 7 (45) , eabj1561. 10.1126/sciadv.abj1561

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Abstract

PAX8 is a key thyroid transcription factor implicated in thyroid gland differentiation and function, and PAX8 gene methylation is reported to be sensitive to the periconceptional environment. Using a novel recall-by-epigenotype study in Gambian children, we found that PAX8 hypomethylation at age 2 years is associated with a 21% increase in thyroid volume and an increase in free thyroxine (T4) at 5 to 8 years, the latter equivalent to 8.4% of the normal range. Free T4 was associated with a decrease in DXA-derived body fat and bone mineral density. Furthermore, offspring PAX8 methylation was associated with periconceptional maternal nutrition, and methylation variability was influenced by genotype, suggesting that sensitivity to environmental exposures may be under partial genetic control. Together, our results demonstrate a possible link between early environment, PAX8 gene methylation and thyroid gland development and function, with potential implications for early embryonic programming of thyroid-related health and disease.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Publisher:	American Association for the Advancement of Science
ISSN:	2375-2548
Date of First Compliant Deposit:	26 January 2022
Date of Acceptance:	16 September 2021
Last Modified:	03 May 2023 13:17
URI:	https://orca.cardiff.ac.uk/id/eprint/146981

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