Associations between Global DNA Methylation and Telomere Length in Healthy Adolescents.
Associations between Global DNA Methylation and Telomere Length in Healthy Adolescents.
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DOI：
10.1038/s41598-017-04493-z
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发表时间：
2017-06-23
影响因子：
4.6
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Dong Y;Huang Y;Gutin B;Raed A;Dong Y;Zhu H
新出现的证据表明，表观遗传学调节成人的端粒动态。然而，儿童和青年中这些途径之间的关系仍不清楚。因此，我们在542名14至18岁的健康青少年(44.8%的非裔美国人；55.2%的女性)中研究了这种相关性。用双抗体夹心法测定总DNA甲基化水平(%5-MC)。白细胞端粒长度定义为端粒与单拷贝基因(T/S)的比值。调整了年龄、性别、种族、坦纳分期、体重指数、PA和批次效应的多元线性回归模型显示，%5 MC与LTL相关(调整后的β = 为0.17，p <； 0.01)。%5 MC解释了LTL5.0%的变异。发现了显著的性别交互作用(p <； 0.01)。在女性中，%5 MC与LTL有关联(所有PS <； 0.01)，但在男性中没有关联。进一步的种族敏感性分析显示，非裔美国人和白人也存在类似的关联(均为PS <； 0.03)。目前的研究首次表明，较低水平的全球DNA甲基化与年轻人的端粒长度较短有关，这可能会降低基因组的稳定性，并增加对疾病的易感性。有必要进行纵向研究，以确定随着时间的推移，全球DNA甲基化对LTL维持的影响。
Emerging evidence suggests that epigenetics regulates telomere dynamics in adults. However, the relationship between these pathways in children and youth remains unknown. Thus, we examined this association in 542 healthy adolescents aged 14 to 18 years old (44.8% African Americans; 55.2% females). Global DNA methylation level (%5-mC) was quantified using ELISA method. Leukocyte telomere length (LTL) was defined as relative telomere to single copy gene (T/S) ratio. Multiple linear regression models, adjusted for age, gender, ethnicity, Tanner stage, BMI, PA, and batch effect, revealed that %5 mC was associated with LTL (adjusted β = 0.17, p < 0.01). %5 mC accounted for 5.0% of the variation for LTL. A significant gender interaction was identified (p < 0.01). There was an association between %5 mC and LTL in females (all ps < 0.01), but not in males. Further sensitivity analyses by race revealed similar associations in African Americans and whites (all ps < 0.03). The present study, for the first time, shows that lower levels of global DNA methylation are associated with shorter telomere lengths in youth, which may decrease genome stability and augment the susceptibility to diseases. Longitudinal studies are warranted to establish the effects of global DNA methylation on LTL maintenance over time.