DNA Methylation at a Nutritionally Sensitive Region of the Gene is Associated with Thyroid Volume and Function in Gambian Children

Overview

Journal Sci Adv

Specialties Biology
Science

Date 2021 Nov 5

PMID 34739318

Citations 8

Authors

Toby Candler

Noah J Kessler

Chathura J Gunasekara

Kate A Ward

Philip James

Eleonora Laritsky

Maria S Baker

Roger Dyer

Rajavel Elango

David Jeffries

Robert A Waterland

Sophie E Moore

Marian Ludgate

Andrew M Prentice

Matt J Silver

Affiliations

Soon will be listed here.

Abstract

PAX8 is a key thyroid transcription factor implicated in thyroid gland differentiation and function, and gene methylation is reported to be sensitive to the periconceptional environment. Using a novel recall-by-epigenotype study in Gambian children, we found that 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 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, gene methylation and thyroid gland development and function, with potential implications for early embryonic programming of thyroid-related health and disease.

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