Salivary epigenetic biomarkers as predictors of emerging childhood obesity

Abstract

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.

DNA methylation in infants with low and high body fatness

“…Interestingly, the influence of FTO gene variant on adiposity appears to be small in infancy but strengthens considerably during childhood [ 38 ]. These results may be reconciled with our results and previous studies which have shown association between adiposity and DNA methylation in older children which include studies of both blood [ 39 , 40 ] and saliva samples [ 41 , 42 ].…”

Regulation of oxytocin receptor gene expression in obsessive–compulsive disorder: a possible role for the microbiota-host epigenetic axis

“…It should be mentioned that the correlation between blood and saliva DNA methylation has not always been reported, due to the high variability in individual cellular composition, even at different time points [73], overall affecting the proportion of white blood cells and buccal keratinocytes [74,75]. However, the use of saliva samples to evaluate DNA methylation as biomarker has been already suggested, for example, for borderline personality disorder [76], schizophrenia [77], stress [78] or as a predictor of childhood obesity [79]. In terms of epigenetic modifications, it has been reported that there is higher correlation between saliva and brain tissues when compared to brain and blood [80].…”

Western Diet: Implications for Brain Function and Behavior

“…Epigenetic changes are produced in these new generations, such as modifications in gene promoters involved in stress and appetite regulation (Schneeberger et al, 2012;Schroeder et al, 2017). Moreover, early adverse childhood experiences could cause DNA methylations in genes associated with obesity (Kaufman et al, 2018;Rushing et al, 2020).…”