DNA methylation of the INSR gene as a mediator of the association between prenatal exposure to famine and adulthood waist circumference

DNA methylation of the INSR gene as a mediator of the association between prenatal exposure to famine and adulthood waist circumference
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INSR 基因的 DNA 甲基化作为产前饥荒暴露与成年腰围之间关联的中介

DOI:
10.1038/s41598-020-69120-w
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发表时间:
2020-07
期刊:
Sci Rep
影响因子:
--
通讯作者:
Jun Ma
Jun Ma
中科院分区:
其他
文献类型:
--
作者:
Zhenghe Wang;Jieyun Song;Changwei Li;Yanhui Li;Luqi Shen;Bin Dong;Zhiyong Zou;Jun Ma

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本研究的目的是探讨INSR和IGF 2基因甲基化是否介导了中国大饥荒的产前暴露与成年期腰围(WC)和BMI的关系。本研究采用多阶段整群随机抽样的方法,从中国饥荒严重省份和邻近饥荒较轻省份共抽取235名研究对象。通过Sequenom的MassARRAY系统检测INSR和IGF 2基因启动子区域的DNA甲基化。使用R的“中介”包来评估DNA甲基化对产前暴露于饥饿与成年WC和BMI之间的关联的中介作用。结果显示,产前饥饿暴露与INSR基因总体甲基化水平升高(d= 3.6%,95%CI 1.2-6.0;P= 0.027)和成年期WC增大(d= 2.72cm; 95%CI 0.20-5.24;P= 0.034)显著相关。此外,饥饿显著增加了四个CpG位点的甲基化水平。CpG 7位点甲基化介导了32.0%(95%CI 5.0- 100.0%,P = 0.029)的产前大饥荒暴露与成年WC之间的关联。总之,INSR的表观遗传变化可能介导了产前饥饿暴露对成年期WC的不利影响。
The aims of this study were to explore whether DNA methylation atINSRandIGF2mediated the association of prenatal exposure to the Chinese great famine with adulthood waist circumference (WC) and BMI. A total of 235 subjects were selected into the present study from severely affected province and a neighbor province with less severely affected famine in China through multi-stage clustered random sampling. DNA methylation at theINSRandIGF2gene promoter regions was detected by the Sequenom’s MassARRAY system. The “mediation” package of R was used to evaluate the mediation effect of DNA methylation on the association between prenatal exposure to the famine and adult WC and BMI. The results showed that prenatal famine exposure was significantly associated with higher overall methylation level of theINSRgene (d= 3.6%; 95% CI 1.2–6.0;P= 0.027) and larger adulthood WC (d= 2.72 cm; 95% CI 0.20–5.24;P= 0.034). Furthermore, famine significantly increased methylation levels at four CpG sites. Methylation of the CpG7 site mediated 32.0% (95% CI 5.0–100.0%,P= 0.029) of the association between prenatal exposure to the Chinese great famine and adulthood WC. In conclusion, Epigenetic changes to theINSRmight mediate the adverse effect of prenatal famine exposure on WC in adulthood.
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