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

Autor: Candler T; MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK., Kessler NJ; Department of Genetics, University of Cambridge, Cambridge, UK., Gunasekara CJ; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Ward KA; MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK.; MRC Lifecourse Epidemiology, University of Southampton, Southampton, UK., James P; Department of Population Health, London School of Hygiene and Tropical Medicine, London, UK., Laritsky E; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Baker MS; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA., Dyer R; British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada., Elango R; British Columbia Children's Hospital Research Institute, Vancouver, BC, Canada., Jeffries D; MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK., Waterland RA; USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA.; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA., Moore SE; MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK.; Department of Women and Children's Health, King's College London, London, UK., Ludgate M; Thyroid Research Group, School of Medicine, Cardiff University, Cardiff, UK., Prentice AM; MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK., Silver MJ; MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK.
Jazyk: angličtina
Zdroj: Science advances [Sci Adv] 2021 Nov 05; Vol. 7 (45), pp. eabj1561. Date of Electronic Publication: 2021 Nov 05.
DOI: 10.1126/sciadv.abj1561
Abstrakt: 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.
Databáze: MEDLINE