Obese children are much more likely than lean individuals to carry a variation in the DNA methylation of a gene that regulates body weight, according to a new study, which will be presented Tuesday at The Endocrine Society’s 92nd Annual Meeting in San Diego.
The findings lend evidence to the theory that obesity risk can increase because of epigenetic alterations—inherited changes in gene expression that, unlike a gene mutation, do not alter the DNA sequence itself, the authors say.
“We observed for the first time in human beings that an epigenetic modification—DNA hypermethylation—is associated with an increased individual risk for the development of obesity,” said lead author Peter Kuehnen, MD, of Germany.
Kuehnen, an endocrinology fellow at Charité Children’s Hospital, Institute of Experimental Pediatric Endocrinology, Berlin, explained that faulty DNA methylation is involved in the development of cancer.
The researchers found that DNA hypermethylation, or excessive methylation, occurs at the pro-opiomelanocortin (POMC) gene, one of the major genes responsible for body weight regulation. A mutation in the POMC gene leads to early-onset extreme obesity but is rare, Kuehnen said.
His group investigated whether, in addition to genetic defects, small variations in DNA sequence, called polymorphisms, might be linked to obesity. Some polymorphisms already identified for diseases predispose people to the development of that disease or protect them from the disease, according to Kuehnen.
The investigators evaluated the DNA methylation pattern on the POMC gene obtained from blood samples from 100 obese children and from 54 healthy-weight children and adults. Many of the obese children, but none of the lean individuals, had DNA hypermethylation at a specific site on the gene, Kuehnen said. This hypermethylation reduced the binding capacity of the p300 protein, which regulates chromatin formation. Chromatin is the protein that packages DNA.
“Although these results have to be confirmed in a much larger study, this hypermethylation polymorphism might alter gene function and might lead to an increased predisposition for obesity later in life,” Kuehnen said.
The investigators plan to study whether the DNA hypermethylation is present in the parents of the obese children and in blood samples from affected children obtained shortly after birth. Such a finding, Kuehnen said, would suggest that this polymorphism is an inherited biomarker for increased risk of obesity.
This study received funding from the German Research Foundation and Germany’s National Genome Research Network. Researchers from the Institute of Human Genetics in Essen, Germany, also participated in the study.
