DNA methylation at a nutritionally sensitive region of the PAX8 gene is associated with thyroid volume and function in Gambian children.
DNA methylation at a nutritionally sensitive region of the PAX8 gene is associated with thyroid volume and function in Gambian children.
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DOI：
10.1126/sciadv.abj1561
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发表时间：
2021-11-05
期刊：
影响因子：
13.6
通讯作者：
Silver MJ
中科院分区：
文献类型：
--
作者：
Candler T;Kessler NJ;Gunasekara CJ;Ward KA;James P;Laritsky E;Baker MS;Dyer R;Elango R;Jeffries D;Waterland RA;Moore SE;Ludgate M;Prentice AM;Silver MJ
儿童PAX8甲基化与甲状腺体积和功能相关，并受母亲围孕期营养的影响。PAX8是甲状腺分化和功能的关键转录因子，PAX8基因甲基化对孕周环境敏感。在冈比亚儿童中使用一项新的表观基因型召回研究，我们发现2岁时PAX8低甲基化与甲状腺体积增加21%和5至8岁时游离甲状腺素（T4）增加相关，后者相当于正常范围的8.4%。游离T4与DXA衍生的体脂和骨密度降低相关。此外，后代PAX8甲基化与围受孕期母体营养相关，甲基化变异受基因型影响，表明对环境暴露的敏感性可能受到部分遗传控制。总之，我们的研究结果表明，早期环境，PAX8基因甲基化和甲状腺发育和功能之间可能存在联系，对甲状腺相关健康和疾病的早期胚胎编程具有潜在意义。
Child PAX8 methylation is associated with thyroid volume and function and influenced by maternal periconceptional nutrition. 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.
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7
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