Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Epigenetics. 2012 Oct;7(10):1133-41. doi: 10.4161/epi.21915. Epub 2012 Aug 23.
Aberrations in global LINE-1 DNA methylation have been related to risk of cancer and cardiovascular disease. Micronutrients including methyl-donors and retinoids are involved in DNA methylation pathways. We investigated associations of micronutrient status and LINE-1 methylation in a cross-sectional study of school-age children from Bogotá, Colombia. Methylation of LINE-1 repetitive elements was quantified in 568 children 5-12 years of age using pyrosequencing technology. We examined the association of LINE-1 methylation with erythrocyte folate, plasma vitamin B12, vitamin A ferritin (an indicator of iron status) and serum zinc concentrations using multivariable linear regression. We also considered associations of LINE-1 methylation with socio-demographic and anthropometric characteristics. Mean (± SD) LINE-1 methylation was 80.25 (± 0.65) percentage of 5-mC (%5-mC). LINE-1 methylation was inversely related to plasma vitamin A. After adjustment for potential confounders, children with retinol levels higher than or equal to 1.05 µmol/L showed 0.19% 5-mC lower LINE-1 methylation than children with retinol levels lower than 0.70 µmol/L. LINE-1 methylation was also inversely associated with C-reactive protein, a marker of chronic inflammation, and female sex. We identified positive associations of maternal body mass index and socioeconomic status with LINE-1 methylation. These associations were not significantly different by sex. Whether modification of these exposures during school-age years leads to changes in global DNA methylation warrants further investigation.
全球 LINE-1 DNA 甲基化的异常与癌症和心血管疾病的风险有关。包括甲基供体和视黄酸在内的微量营养素参与了 DNA 甲基化途径。我们在哥伦比亚波哥大的学龄儿童的横断面研究中调查了微量营养素状态与 LINE-1 甲基化的关联。使用焦磷酸测序技术,我们在 568 名 5-12 岁的儿童中定量了 LINE-1 重复元件的甲基化。我们使用多变量线性回归检验了 LINE-1 甲基化与红细胞叶酸、血浆维生素 B12、维生素 A 铁蛋白(铁状态的指标)和血清锌浓度之间的关联。我们还考虑了 LINE-1 甲基化与社会人口统计学和人体测量特征的关联。LINE-1 甲基化的平均(± SD)为 80.25(± 0.65)为 5-甲基胞嘧啶(%5-mC)的百分比。LINE-1 甲基化与血浆维生素 A 呈负相关。在校正潜在混杂因素后,视黄醇水平高于或等于 1.05 µmol/L 的儿童的 LINE-1 甲基化比视黄醇水平低于 0.70 µmol/L 的儿童低 0.19% 5-mC。LINE-1 甲基化也与 C 反应蛋白呈负相关,C 反应蛋白是慢性炎症的标志物,与女性性别呈负相关。我们发现母亲的体重指数和社会经济地位与 LINE-1 甲基化呈正相关。这些关联在性别之间没有显著差异。在校龄期间对这些暴露的修饰是否会导致全基因组 DNA 甲基化的变化,值得进一步研究。