BACKGROUND Epigenetics could facilitate greater understanding of disparities in the emergence of childhood obesity. While blood is a common tissue used in human epigenetic studies, saliva is a promising tissue. Our prior findings in non-obese preschool-aged Hispanic children identified 17 CpG dinucleotides for which differential methylation in saliva at baseline was associated with maternal obesity status. The current study investigated to what extent baseline DNA methylation in salivary samples in these 3-5-year-old Hispanic children predicted the incidence of childhood obesity in a 3-year prospective cohort. METHODS We examined a subsample (n = 92) of Growing Right Onto Wellness (GROW) trial participants who were randomly selected at baseline, prior to randomization, based on maternal phenotype (obese or non-obese). Baseline saliva samples were collected using the Oragene DNA saliva kit. Objective data were collected on child height and weight at baseline and 36 months later. Methylation arrays were processed using standard protocol. Associations between child obesity at 36 months and baseline salivary methylation at the previously identified 17 CpG dinucleotides were evaluated using multivariable logistic regression models. RESULTS Among the n = 75 children eligible for analysis, baseline methylation of Cg1307483 (NRF1) was significantly associated with emerging childhood obesity at 36-month follow-up (OR = 2.98, p = 0.04), after adjusting for child age, gender, child baseline BMI-Z, and adult baseline BMI. This translates to a model-estimated 48% chance of child obesity at 36-month follow-up for a child at the 75th percentile of NRF1 baseline methylation versus only a 30% chance of obesity for a similar child at the 25th percentile. Consistent with other studies, a higher baseline child BMI-Z during the preschool period was associated with the emergence of obesity 3 years later, but baseline methylation of NRF1 was associated with later obesity even after adjusting for child baseline BMI-Z. CONCLUSIONS Saliva offers a non-invasive means of DNA collection and epigenetic analysis. Our proof of principle study provides sound empirical evidence supporting DNA methylation in salivary tissue as a potential predictor of subsequent childhood obesity for Hispanic children. NFR1 could be a target for further exploration of obesity in this population.

中文翻译：

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唾液表观遗传标志物可预测儿童肥胖的发生。

背景技术表观遗传学可以促进对儿童肥胖出现中的差异的更多理解。血液是人类表观遗传研究中常用的组织，而唾液是有希望的组织。我们在非肥胖学龄前的西班牙裔儿童中的先前发现确定了17个CpG二核苷酸，其基线时唾液中的甲基化差异与母亲肥胖状况有关。本研究调查了这些3-5岁西班牙裔儿童唾液样本中基线DNA甲基化程度在多大程度上预测了3岁前瞻性队列中儿童肥胖的发生率。方法我们研究了根据健康状况（肥胖或非肥胖）在随机分组之前于基线随机选择的健康成长权（GROW）试验参与者的子样本（n = 92）。使用Oragene DNA唾液试剂盒收集基线唾液样品。在基线和36个月后收集关于儿童身高和体重的客观数据。使用标准方案处理甲基化阵列。使用多变量逻辑回归模型评估了36个月大的儿童肥胖与先前确定的17个CpG二核苷酸的基线唾液甲基化之间的关联。结果在符合条件的75例儿童中，经过36个月的随访（校正了儿童的年龄，性别，儿童基线BMI-Z和成人基线BMI。在NRF1基线甲基化水平为第75个百分位的孩子，在36个月的随访中，该模型可得出模型估计的儿童肥胖的机会为48％，而在第25个百分位的类似儿童，其肥胖的机会仅为30％。与其他研究一致，学龄前儿童基线BMI-Z较高与3年后肥胖的出现有关，但是即使在调整了儿童基线BMI-Z之后，NRF1的基线甲基化也与后来的肥胖有关。结论唾液提供了DNA采集和表观遗传分析的非侵入性手段。我们的原理研究证明提供了可靠的经验证据，支持唾液组织中的DNA甲基化可作为西班牙裔儿童随后发生肥胖症的潜在预测指标。NFR1可能是进一步探索肥胖人群的目标。