Researchers have found a molecular marker in saliva that has been linked to childhood obesity in a group of preschool-aged Hispanic children.
Research published in BMC Medical Genetics supports the ongoing efforts to identify biomarkers associated with the emergence of childhood obesity before body mass index (BMI) is designated as obese.
Tackling obesity in Hispanic children before it occurs
Shari Barkin, William K. Warren Foundation, Professor of Medicine and chief of the Division of General Paediatrics explained that: “Understanding the factors that predispose children to obesity is important and will pave the way toward better prevention and early intervention.”
Hispanic populations are burdened with a disproportionate risk when it comes to the obesity crisis. Paediatric obesity has been increasing at an alarming rate and is associated with the onset of later comorbidities including type 2 diabetes, high blood pressure and cancer.
Looking for biomarkers that allow intervention earlier
Barkin said: “Right now, we only have crude markers to predict the emergence of obesity; we wait until the BMI is a certain number to intervene. We’re looking for markers that will allow us to intervene much earlier.”
Over a three-year study period, baseline saliva samples were collected from children who were enrolled in the Growing Right onto Wellness (GROW) trial and were at-risk for obesity, but not yet obese. A total of 610 parent-preschool child pairs were included in the study, 90% of whom were Hispanic, received high-dose behavioural intervention over the three years.
The investigators had collected saliva as an easily accessible, non-invasive tissue that they hoped would reveal genetic and epigenetic factors that might predispose a child to obesity.
Shedding light on behaviour and genetics
Barkin explained: “Even though many of the children in our intervention group compared to our control group improved their nutrition, maintained physical activity consistent with guidelines and got sufficient sleep, 30% of them still emerged into obesity. This sheds new light on how we think about the interaction of behaviour and genetics and how that might contribute to health disparities.”
In a previous study, the researchers analysed saliva samples from a subset of the enrolled children for methylation of genes associated with obesity.
Methylation is an epigenetic “mark” on DNA that regulates gene expression. They found that methylation at 17 DNA sites in the child’s baseline saliva was associated with the mother’s BMI and waist circumference, suggesting that obesity risk may be transmitted from mother to child.
Linking saliva to BMI
Now, they have evaluated associations between baseline salivary methylation and objective changes in child BMI after three years in the study.
Barkin explained: “At baseline, these children were all non-obese, but based on their maternal BMI, their DNA was methylated differently at 17 sites. 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 behavioural factors?'”
The research team discovered that methylation of a gene called NRF1, which has roles in adipose tissue inflammation, was associated with childhood obesity. Therefore, a child with the NRF1 methylation at baseline had a threefold increased odds of being obese three years later, after controlling for maternal BMI and other factors.
“This is a proof-of-principle study; it needs to be repeated with larger numbers of children,” Barkin stated. “But even with small numbers, we found a really important signal using salivary epigenetics.”
The benefits of using saliva for epigenetic studies
The research demonstrates the effectiveness of using saliva for epigenetic studies and points to at least one gene, NRF1, that should be more extensively studied for its role in the emergence of obesity.
Barkin noted: “Most studies have looked for factors in children who are already obese, 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.”
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