Title
Identification of mutations in the NUCB2/nesfatin gene in children with severe obesity Identification of mutations in the NUCB2/nesfatin gene in children with severe obesity
Author
Faculty/Department
Faculty of Medicine and Health Sciences
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences . Biomedical Sciences
University Hospital Antwerp
Publication type
article
Publication
Orlando, Fla ,
Subject
Chemistry
Biology
Human medicine
Source (journal)
Molecular genetics and metabolism. - Orlando, Fla
Volume/pages
107(2012) :4 , p. 729-734
ISSN
1096-7192
ISI
000311816200016
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
Nesfatin-1 is the N-terminal fragment of nucleobindin-2 (NUCB2) that was identified as a novel satiety molecule in rodents. The protein is reported to exert anorexigenic effects and appears to play an important role in hypothalamic pathways regulating energy homeostasis and food intake. In this study, we hypothesized that mutations in the nesfatin encoding gene NUCB2 might cause obesity in humans. Therefore, we screened the entire coding region of the NUCB2 gene for mutations in a population of 471 obese children and adolescents. Mutation analysis of NUCB2 identified a total of seven sequence variants of which four were previously reported as polymorphisms. The remaining three variants included ex9 + 6G>C, L125H and K178X and were found in 3 unrelated individuals in the obese population only (0.6%). Biochemical experiments including ELISA and western blot were performed on plasma samples of the obese patient carrying the nonsense mutation K178X However, neither NUCB2/nesfatin-1 immunoreactive plasma levels of the patient, nor expression of full length NUCB2 differed significantly from matched obese control individuals. In conclusion, we have identified the first genetic variants in the NUCB2 gene in obese individuals, although further functional characterization will be essential to verify disease causality of the mutations. (C) 2012 Elsevier Inc. All rights reserved.
E-info
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