Biomarkers in saliva could predict childhood obesity rates, according to a proof-of-principle study published in BMC Medical Genetics.
Led by Shari Barkin, M.D., director of Pediatric Obesity Research at Monroe Carell Jr. Children’s Hospital at Vanderbilt, the three-year study showed a distinct DNA methylation pattern was associated with the emergence of obesity in preschool-aged children. The findings build on Barkin’s previous work connecting the methylation pattern to maternal body mass index (BMI).
“Our study demonstrates that there are already changes in the physiology — a pathway to obesity — even before the phenotype of obesity emerges. If we can define a predictive epigenetic signature, we can intervene earlier to reduce health disparities in common conditions like obesity,” Barkin said.
“There are already changes in the physiology — a pathway to obesity — even before the phenotype of obesity emerges.”
Children at High Risk
The prevalence of pediatric obesity has been increasing at an alarming rate, with a disproportionate burden in Hispanic populations, Barkin said. Pediatric obesity is associated with the onset of later comorbidities including type 2 diabetes and sleep apnea.
“Right now, we only have crude markers to predict the emergence of obesity; we wait until the BMI is a certain number to intervene,” Barkin said. “We’re looking for markers that will allow us to intervene much earlier.”
Clues in Saliva
Saliva offers a practical source for biomarkers, particularly for children wary of needles and blood. Barkin’s biomarker of interest is a 17 CpG dinucleotide methylation pattern in the gene NRF1.
Barkin’s team looked for the epigenetic pattern in saliva from 75 Hispanic children (ages three to five) enrolled in the Growing Right Onto Wellness (GROW) trial. Then, the researchers measured each child’s BMI three years later.
“At baseline, these children were all non-obese, but based on their maternal BMI, their DNA was methylated differently at 17 sites,” Barkin said. “Now we know that some of them emerged into obesity. We asked, ‘Could we have predicted that from differences in methylation, even after accounting for maternal BMI and assessing other behavioral factors?’”
Study results confirmed a link between obesity at three years to baseline NRF1 methylation. The researchers’ model estimated a 48 percent chance of obesity at three years for a child at the 75th percentile of NRF1 methylation, versus only a 30 percent chance of obesity for a similar child at the 25th percentile.
“Understanding the factors that predispose children to obesity is important and will pave the way toward better prevention and early intervention.”
A Novel Predictor
The study is the first of its kind and demonstrates that saliva could be a non-invasive source for epigenetic information related to a child’s obesity risk. Said Barkin, “Most studies have looked for [risk] factors in children who are already obese.”
“Understanding the factors that predispose children to obesity is important and will pave the way toward better prevention and early intervention,” Barkin added. “This is a proof-of-principle study; it needs to be repeated with larger numbers of children. But even with small numbers, we found a really important signal using salivary epigenetics.”
