ABSTRACT

Mistimed sleep/wake and eating patterns put shift workers at increased risk for cardiometabolic disease, and epigenetic modification of circadian genes has been proposed as a mechanism. Although not as extreme as shift workers, adolescents often have delayed sleep timing and irregular eating patterns. The aim was to assess whether sleep midpoints – median of bed and wake time – and dietary patterns in adolescents were associated with DNA methylation of circadian genes. The study population included 142 Mexican youth (average age of 14.0 (SD = 2.0) years, 49% male). Average sleep midpoint over weekdays was estimated with actigraphy. Diet was assessed with a semi-quantitative food frequency questionnaire, and three dietary patterns were derived from principal component analysis, a Plant-based & lean proteins pattern, a Meat & starchy pattern, and an Eggs, milk & refined grain pattern. DNA methylation was quantified in blood leukocytes with the Infinium MethylationEPIC BeadChip, and data from 548 CpG sites within 12 circadian genes were examined. Linear regression analyses, adjusted for sex, age, and % monocytes, showed that later sleep timing was associated with higher DNA methylation of several circadian genes, notably with RORB, PER1, CRY2, and NR1D1. Each of the dietary patterns examined was also related to circadian gene DNA methylation, but the Eggs, milk & refined grain pattern (‘breakfast’ pattern) had the clearest evidence of relationships with circadian genes, with inverse associations (lower DNA methylation) across all 12 genes. Findings suggest that timing-related sleep and eating behaviours among adolescents could result in epigenetic modification of clock genes.

摘要

不合时宜的睡眠/觉醒和饮食模式使轮班工人患心脏代谢疾病的风险增加，昼夜节律基因的表观遗传修饰已被提议作为一种机制。虽然不像轮班工人那样极端，但青少年经常会延迟睡眠时间和不规律的饮食习惯。目的是评估青少年的睡眠中点（睡觉和醒来时间的中位数）和饮食模式是否与昼夜节律基因的 DNA 甲基化相关。研究人群包括 142 名墨西哥青年（平均年龄 14.0 (SD = 2.0) 岁，49% 为男性）。工作日的平均睡眠中点是用活动记录仪估计的。使用半定量食物频率问卷评估饮食，并从主成分分析中得出三种饮食模式，植物性蛋白质和瘦肉蛋白模式、肉类和淀粉模式以及鸡蛋、牛奶和精制谷物模式。使用 Infinium MethylationEPIC BeadChip 对血液白细胞中的 DNA 甲基化进行了量化，并检查了 12 个昼夜节律基因中 548 个 CpG 位点的数据。针对性别、年龄和单核细胞百分比进行调整的线性回归分析表明，较晚的睡眠时间与多个昼夜节律基因的较高 DNA 甲基化相关，尤其是RORB、PER1、CRY2和NR1D1。所检查的每一种饮食模式也与昼夜节律基因 DNA 甲基化有关，但鸡蛋、牛奶和精制谷物模式（“早餐”模式）最清楚地证明了与昼夜节律基因的关系，所有 12 个基因都具有反向关联（较低的 DNA 甲基化）。研究结果表明，青少年与时间相关的睡眠和饮食行为可能导致时钟基因的表观遗传修饰。