Louisiana State University Health Sciences Center, School of Medicine, 1901 Perdido Street, New Orleans, LA, 70112, USA.
Department of Pediatrics, Vanderbilt University Medical Center, 2146 Belcourt Ave, Nashville, TN, 37232-9225, USA.
BMC Med Genet. 2020 Feb 14;21(1):34. doi: 10.1186/s12881-020-0968-7.
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.
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.
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.
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.
表观遗传学可以帮助我们更好地理解儿童肥胖的出现存在差异的原因。虽然血液是人类表观遗传学研究中常用的组织，但唾液也是一种很有前途的组织。我们之前在非肥胖的学龄前西班牙裔儿童中发现了 17 个 CpG 二核苷酸，这些二核苷酸在基线时唾液中的差异甲基化与母亲肥胖状况有关。目前的研究调查了这些 3-5 岁西班牙裔儿童的唾液样本中基线时的 DNA 甲基化在多大程度上预测了他们在 3 年前瞻性队列研究中发生儿童肥胖的情况。
我们检查了 Growing Right Onto Wellness（GROW）试验的一个亚样本（n=92），这些参与者是在随机分组前根据母亲的表型（肥胖或非肥胖）随机选择的。使用 Oragene DNA 唾液试剂盒收集基线时的唾液样本。在基线和 36 个月后收集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在之前确定的 17 个 CpG 二核苷酸处，儿童在 36 个月时肥胖与基线唾液甲基化之间的关系。
在 n=75 名符合分析条件的儿童中，Cg1307483（NRF1）的基线甲基化与 36 个月随访时出现的儿童肥胖显著相关（OR=2.98，p=0.04），调整了儿童年龄、性别、儿童基线 BMI-Z 和成人基线 BMI 后。这意味着，对于 NRF1 基线甲基化处于第 75 百分位数的儿童，根据模型估计，他们在 36 个月随访时肥胖的可能性为 48%，而对于基线甲基化处于第 25 百分位数的类似儿童，肥胖的可能性仅为 30%。与其他研究一致，学龄前期间较高的基线儿童 BMI-Z 与 3 年后肥胖的发生有关，但即使调整了儿童基线 BMI-Z，NRF1 的基线甲基化与后来的肥胖有关。
唾液提供了一种非侵入性的 DNA 采集和表观遗传分析方法。我们的原理验证研究为唾液组织中的 DNA 甲基化作为西班牙裔儿童随后发生儿童肥胖的潜在预测因子提供了可靠的经验证据。NFR1 可能是该人群中肥胖进一步研究的一个目标。
