Screening for genetic variants in BDNF that contribute to childhood obesity
Version of Record online: 16 JAN 2013
© 2012 The Authors. Pediatric Obesity © 2012 International Association for the Study of Obesity
Volume 9, Issue 1, pages 36–42, February 2014
How to Cite
Zegers, D., Hendrickx, R., Verrijken, A., Van Hoorenbeeck, K., Van Camp, J. K., de Craemer, V., Rooman, R. P., Desager, K. N., Massa, G., Van Gaal, L. F., Van Hul, W. and Beckers, S. (2014), Screening for genetic variants in BDNF that contribute to childhood obesity. Pediatric Obesity, 9: 36–42. doi: 10.1111/j.2047-6310.2012.00131.x
- Issue online: 21 JAN 2014
- Version of Record online: 16 JAN 2013
- Manuscript Accepted: 5 NOV 2012
- Manuscript Revised: 29 OCT 2012
- Manuscript Received: 4 MAY 2012
- Institute for the Promotion of Innovation through Science and Technology in Flanders (IWT-Vlaanderen)
- Flemish Fund for Scientific Research (F.W.O. Vlaanderen)
- Fonds voor Wetenschappelijk Onderzoek Vlaanderen. Grant Number: G0028.05
- TOP-research grant from the University of Antwerp
- childhood obesity;
- genetic variants;
- melanocortin signalling
- BDNF is involved in the regulation of food intake and body weight.
- BDNF deficient animal models are obese.
- Chromosomal abnormalities cause obesity in humans.
- Evaluation of point mutations in BDNF.
- Identification of BDNF mutations in obese children.
- Point mutations in BDNF are not a common cause of childhood obesity.
There is ample evidence that BDNF has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that BDNF deficiency leads to the development of obesity. Functional loss of one copy of the BDNF gene, due to chromosomal rearrangements or microdeletions, can cause an obesity phenotype in humans. Therefore, we wanted to investigate whether point mutations in the gene also result in a comparable phenotype.
We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of BDNF. Mutation screening was performed by high-resolution melting curve analysis and direct sequencing.
Screening of obese patients led to the identification of two synonymous variations (V37V and H65H) and two non-synonymous coding mutations (T2I and V46M) in the BDNF gene. When we subsequently screened our control population, we found T2I with comparable frequency and confirmed that this is a rare and non-pathogenic variant. In addition, we found another non-synonymous mutation (N187S) in the control population.
In silico analysis of the V46M variant did not support a clear disease-causing effect and no family data were available in order to determine whether the mutation segregates with obesity. However, we cannot rule out a possible pathogenic effect for this variant. In general, we tend to conclude that mutations in the coding region of BDNF are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.