Screening for genetic variants in BDNF that contribute to childhood obesity. Issue 1 (16th January 2013)

• Record Type: Journal Article
• Authors: Zegers, D.; Hendrickx, R.; Verrijken, A.; Van Hoorenbeeck, K.; Van Camp, J. K.; de, V.; Rooman, R. P.; Desager, K. N.; Massa, G.; Van Gaal, L. F.; Van Hul, W.; Beckers, S.
• Is Part Of: Pediatric obesity. Volume 9:Issue 1(2014:Feb.)
• Page Start: 36
• Page End: 42
• Publication Date: 2013-01-16
• Subjects: Obesity in children -- Periodicals; Obesity in adolescence -- Periodicals; Obesity -- Periodicals; Overweight children -- Periodicals; 618.92398
• DOI: 10.1111/j.2047-6310.2012.00131.x
• Languages: English
• ISSNs: 1747-7174

Abstract

<abstract abstract-type="main"> <title>Summary</title> <sec id="ijpo131-sec-0001" sec-type="section"> <p> <list id="ijpo131-list-0001" list-type="bullet"> <title>What is already known about this subject</title> <list-item> <p> BDNF is involved in the regulation of food intake and body weight.</p> </list-item> <list-item> <p> BDNF deficient animal models are obese.</p> </list-item> <list-item> <p> Chromosomal abnormalities cause obesity in humans.</p> </list-item> </list> </p> </sec> <sec id="ijpo131-sec-0002" sec-type="section"> <p> <list id="ijpo131-list-0002" list-type="bullet"> <title>What this study adds</title> <list-item> <p> Evaluation of point mutations in BDNF.</p> </list-item> <list-item> <p> Identification of BDNF mutations in obese children.</p> </list-item> <list-item> <p> Point mutations in BDNF are not a common cause of childhood obesity.</p> </list-item> </list> </p> </sec> <sec id="ijpo131-sec-0003" sec-type="section"> <title>Introduction</title> <p>There is ample evidence that <italic>BDNF</italic> has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that <italic>BDNF</italic> deficiency leads to the development of obesity. Functional loss of one copy of the <italic>BDNF</italic> 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.</p> </sec> <sec id="ijpo131-sec-0004" sec-type="section"> <title>Methods</title> <p>We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of <italic>BDNF</italic>. Mutation screening was performed by high‐resolution melting curve analysis and direct sequencing.</p> </sec> <sec id="ijpo131-sec-0005" sec-type="section"> <title>Results</title> <p>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 <italic>BDNF</italic> 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.</p> </sec> <sec id="ijpo131-sec-0006" sec-type="section"> <title>Conclusions</title> <p> <italic>In silico</italic> 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 <italic>BDNF</italic> are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.</p> </sec> </abstract>