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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.

SUBMITTER: Rushing A

PROVIDER: S-EPMC7023819 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Salivary epigenetic biomarkers as predictors of emerging childhood obesity.

Rushing Amanda A Sommer Evan C EC Zhao Shilin S Po'e Eli K EK Barkin Shari L SL

BMC medical genetics 20200214 1

<h4>Background</h4>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 ...[more]

PMID: 32059710

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Project description:Obesity can increase the risk of complex metabolic diseases, including insulin resistance. Moreover, obesity can be caused by environmental and genetic factors. However, the epigenetic mechanisms of obesity are not well defined. Therefore, the identification of novel epigenetic biomarkers of obesity allows for a more complete understanding of the disease and its underlying insulin resistance. The aim of our study was to identify DNA methylation changes in whole-blood that were strongly associated with obesity and insulin resistance. Whole-blood was obtained from lean (n = 10; BMI = 23.6 ± 0.7 kg/m2) and obese (n = 10; BMI = 34.4 ± 1.3 kg/m2) participants in combination with euglycemic hyperinsulinemic clamps to assess insulin sensitivity. We performed reduced representation bisulfite sequencing on genomic DNA isolated from the blood. We identified 49 differentially methylated cytosines (DMCs; q < 0.05) that were altered in obese compared with lean participants. We identified 2 sites (Chr.21:46,957,981 and Chr.21:46,957,915) in the 5' untranslated region of solute carrier family 19 member 1 (SLC19A1) with decreased methylation in obese participants (lean 0.73 ± 0.11 vs. obese 0.09 ± 0.05; lean 0.68 ± 0.10 vs. obese 0.09 ± 0.05, respectively). These 2 DMCs identified by obesity were also significantly predicted by insulin sensitivity (r = 0.68, P = 0.003; r = 0.66; P = 0.004). In addition, we performed a differentially methylated region (DMR) analysis and demonstrated a decrease in methylation of Chr.21:46,957,915-46,958,001 in SLC19A1 of -34.9% (70.4% lean vs. 35.5% obese). The decrease in whole-blood SLC19A1 methylation in our obese participants was similar to the change observed in skeletal muscle (Chr.21:46,957,981, lean 0.70 ± 0.09 vs. obese 0.31 ± 0.11 and Chr.21:46,957,915, lean 0.72 ± 0.11 vs. obese 0.31 ± 0.13). Pyrosequencing analysis further demonstrated a decrease in methylation at Chr.21:46,957,915 in both whole-blood (lean 0.71 ± 0.10 vs. obese 0.18 ± 0.06) and skeletal muscle (lean 0.71 ± 0.10 vs. obese 0.30 ± 0.11). Our findings demonstrate a new potential epigenetic biomarker, SLC19A1, for obesity and its underlying insulin resistance.

Project description:IntroductionThe objective of this study was to identify predictors of severe obesity in a low-income, predominantly Hispanic/Latino sample of children in Texas.MethodsThis cross-sectional analysis examined baseline data on 517 children from the secondary prevention component of the Texas Childhood Obesity Research Demonstration (TX CORD) study; data were collected from September 2012 through February 2014. Self-administered surveys were used to collect data from parents of children who were aged 2 to 12 years, had a body mass index (BMI) in the 85th percentile or higher, and resided in Austin, Texas, or Houston, Texas. Multivariable logistic regression models adjusted for sociodemographic covariates were used to examine associations of children's early-life and maternal factors (large-for-gestational-age, exclusive breastfeeding for ≥4 months, maternal severe obesity [BMI ≥35.0 kg/m2]) and children's behavioral factors (fruit and vegetable consumption, physical activity, screen time) with severe obesity (BMI ≥120% of 95th percentile), by age group (2-5 y, 6-8 y, and 9-12 y).ResultsAcross all ages, 184 (35.6%) children had severe obesity. Among children aged 9 to 12 years, large-for-gestational-age at birth (odds ratio [OR] = 2.31; 95% confidence interval [CI], 1.13-4.73) was significantly associated with severe obesity. Maternal severe obesity was significantly associated with severe obesity among children aged 2 to 5 years (OR = 2.67; 95% CI, 1.10-6.47) and 9 to 12 years (OR = 4.12; 95% CI, 1.84-9.23). No significant association was observed between behavioral factors and severe obesity in any age group.ConclusionIn this low-income, predominantly Hispanic/Latino sample of children, large-for-gestational-age and maternal severe obesity were risk factors for severe obesity among children in certain age groups. Promoting healthy lifestyle practices during preconception and prenatal periods could be an important intervention strategy for addressing childhood obesity.

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Salivary epigenetic biomarkers as predictors of emerging childhood obesity.

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Salivary epigenetic biomarkers as predictors of emerging childhood obesity.

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