Single gene variation may lead to obesity, study finds

Washington: Researchers have identified a single variation in a gene that influences obesity in children and adults by lowering the levels of a certain protein that helps us feel full. The study suggests that a less common version of the brain-derived neurotropic factor (BDNF) gene may predispose people to obesity by producing lower levels of BDNF protein, a regulator of appetite, in the brain.

The researchers propose that boosting BDNF protein levels may offer a therapeutic strategy for people with the genetic variation, which tends to occur more frequently in African Americans and Hispanics, than in non-Hispanic Caucasians. "This study explains how a single genetic change in BDNF influences obesity and may affect BDNF protein levels. Finding people with specific causes of obesity may allow us to evaluate effective, more-personalised treatments," said Jack A Yanovski, an investigator at US National Institute of Child Health and Human Development (NICHD).

The BDNF protein plays several roles in the brain and nervous system and, at high levels, the protein can stimulate the feeling of fullness. The researchers identified an area of the gene where a single change reduced BDNF levels in the hypothalamus, a key area that controls eating and body weight. The genetic change the researchers identified was not a rare mutation, but rather a variation that occurs in the general population. Every person has two copies, or alleles, of each gene, inheriting one copy from each parent. In their study, the researchers referred to the common allele as "T," and the less common allele, which produces less BDNF protein, as "C."

They studied the BDNF gene in four groups of people, more than 31,000 males and females. They compared a person's BDNF gene combination - CC, CT or TT - to factors that define obesity, such as body mass index (BMI) and percentage of body fat. In African American adults, the team found that the C allele was associated with higher BMI and body fat percentage in those with CT or CC types. In a group of healthy children of many races, the researchers found that CC types had higher BMI scores and percentage of body fat when compared to CT or TT types, who were similar to each other.

Finally, in a group of Hispanic children, the researchers found that the C allele (CT, CC types) was associated with a higher BMI score. Overall, the study suggests that the C allele of the BDNF gene may be linked to obesity in people. "Lower BDNF levels may contribute to obesity in people with the C allele. If these findings are supported by additional studies, boosting BDNF levels may prove beneficial," said Joan C Han, a former NICHD investigator now at the University of Tennessee Health Science Center, who led the study. The study was published in the journal Cell Reports.