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, Silver Matt J
MRC Unit The Gambia at the London School of Hygiene and Tropical Medicine, London, UK.
Department of Genetics, University of Cambridge, Cambridge, UK.
Sci Adv. 2021 Nov 5;7(45):eabj1561. doi: 10.1126/sciadv.abj1561.
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.
PAX8是一种关键的甲状腺转录因子，与甲状腺的分化和功能有关，并且据报道基因甲基化对受孕前后的环境敏感。通过在冈比亚儿童中进行的一项新颖的基于表观基因型的回顾性研究，我们发现2岁时的低甲基化与5至8岁时甲状腺体积增加21%以及游离甲状腺素（T4）增加有关，后者相当于正常范围的8.4%。游离T4与双能X线吸收法（DXA）测定的体脂和骨矿物质密度降低有关。此外，子代甲基化与受孕前后母亲的营养状况有关，甲基化变异性受基因型影响，这表明对环境暴露的敏感性可能部分受基因控制。总之，我们的结果表明早期环境、基因甲基化与甲状腺发育和功能之间可能存在联系，这对甲状腺相关健康和疾病的早期胚胎编程具有潜在影响。
