Effect of prenatal bisphenol A exposure on early childhood body mass index through epigenetic influence on the insulin-like growth factor 2 receptor (IGF2R) gene,Environment International

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Effect of prenatal bisphenol A exposure on early childhood body mass index through epigenetic influence on the insulin-like growth factor 2 receptor (IGF2R) gene
Environment International ( IF 10.3 ) Pub Date : 2020-07-06 , DOI: 10.1016/j.envint.2020.105929
Yoon-Jung Choi ₁ , Young Ah Lee ₂ , Yun-Chul Hong ₃ , Jinwoo Cho ₄ , Kyung-Shin Lee ₁ , Choong Ho Shin ₂ , Bung-Nyun Kim ₅ , Johanna Inhyang Kim ₆ , Soo Jin Park ₇ , Hans Bisgaard ₈ , Klaus Bønnelykke ₈ , Youn-Hee Lim ₉

Affiliation

Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Environmental Health Center, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Department of Pediatrics, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.
Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Environmental Health Center, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea.
Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea.
Division of Children and Adolescent Psychiatry, Department of Psychiatry, Seoul National University Hospital, Seoul 03080, Republic of Korea.
Department of Psychiatry, Hanyang University Medical Center, Seoul 04763, Republic of Korea.
Department of Surgery, Wonkwang University Sanbon Hospital, Gunpo 15865, Republic of Korea.
COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen, 2820, Gentofte, Copenhagen, Denmark.
Institute of Environmental Medicine, Seoul National University Medical Research Center, Seoul 03080, Republic of Korea; Section of Environmental Epidemiology, Department of Public Health, University of Copenhagen, Copenhagen 1014, Denmark.

Epigenetic mechanisms have been suggested to play a role in the link between exposure to bisphenol A (BPA) and pediatric obesity; however, there is little evidence regarding this mechanism in humans. We obtained data on obesity-associated CpG sites from a previous epigenome-wide association study, and then examined whether methylation at those CpG sites was influenced by prenatal BPA exposure. We then evaluated the relationship between CpG methylation status and body mass index (BMI) in a prospective children’s cohort at ages 2, 4, 6, and 8 years. Methylation profiles of 59 children were longitudinally analyzed at ages 2 and 6 years using the Infinium Human Methylation BeadChip. A total of 594 CpG sites known to be BMI or obesity-associated sites were tested for an association with prenatal BPA levels, categorized into low and high exposure groups based on the 80th percentile of maternal BPA levels (2.68 μg/g creatinine), followed by an analysis of the association between DNA methylation and BMI from ages 2–8. There was a significant increase in the methylation levels of cg19196862 () in the high BPA group at age 2 years ( = 0.00030, false discovery rate corrected < 0.10) but not at age 6. With one standard deviation increase of methylation at cg19196862 () at age 2 years, the linear mixed model analysis revealed that BMI during ages 2–8 years significantly increased by 0.49 (95% confidence interval; 0.08, 0.90) in girls, but not in boys. The indirect effect of prenatal BPA exposure on early childhood BMI through methylation at cg19196862 () at age 2 years was marginally significant. Prenatal exposure to BPA may influence differential methylation of at age 2. This result indicates that a possible sensitive period of DNA methylation occurs earlier during development, which may affect BMI until later childhood in a sex-specific manner.

中文翻译：

产前双酚 A 暴露通过对胰岛素样生长因子 2 受体 (IGF2R) 基因的表观遗传影响对儿童早期体重指数的影响

研究表明，表观遗传机制在接触双酚 A (BPA) 与儿童肥胖之间的联系中发挥着重要作用；然而，几乎没有证据表明人类存在这种机制。我们从之前的表观基因组范围关联研究中获得了与肥胖相关的 CpG 位点的数据，然后检查了这些 CpG 位点的甲基化是否受到产前 BPA 暴露的影响。然后，我们在 2、4、6 和 8 岁的前瞻性儿童队列中评估了 CpG 甲基化状态与体重指数 (BMI) 之间的关系。使用 Infinium 人类甲基化珠芯片对 59 名 2 岁和 6 岁儿童的甲基化谱进行了纵向分析。总共测试了 594 个已知与 BMI 或肥胖相关的 CpG 位点与产前 BPA 水平的关联，根据母体 BPA 水平的第 80 个百分位（2.68 μg/g 肌酐）分为低暴露组和高暴露组，然后通过分析 2-8 岁 DNA 甲基化与 BMI 之间的关联。高 BPA 组的 cg19196862 () 甲基化水平在 2 岁时显着增加（= 0.00030，错误发现率校正 < 0.10），但在 6 岁时则没有。cg19196862 () 甲基化水平增加一个标准差在 2 岁时，线性混合模型分析显示，女孩 2-8 岁时的 BMI 显着增加了 0.49（95% 置信区间；0.08，0.90），但男孩则没有。产前 BPA 暴露通过 2 岁时 cg19196862 () 甲基化对幼儿 BMI 产生间接影响，但影响轻微。产前接触 BPA 可能会影响 2 岁时的差异甲基化。这一结果表明，DNA 甲基化的敏感期可能发生在发育早期，这可能会以性别特异性的方式影响直到童年后期的 BMI。

更新日期：2020-07-06

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