ECE2015 Guided Posters Diabetes and obesity – Translational cardiovascular and obesity (8 abstracts)
Screening for genetic and structural variation in the NPY2R gene in obese children and adolescents
Evi Aerts , Doreen Zegers 1 , Laure Sorber 1 , Sigri Beckers 1 , An Verrijken 2 , Guy Massa 3 , Kim Van Hoorenbeeck 4 , Stijn L Verhulst 4 , Luc F Van Gaal 2 & Wim Van Hul 1
1Department of Medical Genetics, University of Antwerp, Antwerp, Belgium; 2Department of Endocrinology, Diabetology and Metabolic Diseases, Antwerp University Hospital, Antwerp, Belgium; 3Department of Pediatrics, Jessa Hospital, Hasselt, Belgium; 4Department of Pediatrics, Antwerp University Hospital, Antwerp, Belgium.
Objective: NPY2R is a G-protein-coupled receptor which is highly expressed in orexigenic NPY/AGRP neurons within the arcuate nucleus, a major integrator of appetite control in the hypothalamus. Genetic evidence coming from animal and association studies, has identified NPY2R as a candidate gene for obesity. Therefore we have designed an extensive mutation and CNV-analysis investigating the prevalence of genetic and structural variation in NPY2R.
Design and methods: In the first part of this study we screened 306 obese children and adolescents and 300 healthy lean individuals for mutations in the NPY2R coding region with high-resolution melting curve analysis. Direct sequencing was performed for samples with melting patterns deviating from WT. In the second part of this study, Multiplex Amplicon Quantification (MAQ) analysis was performed in 308 obese children and adolescents to detect copy number variation (CNV) in NPY2R.
Results: Mutation analysis resulted in the identification of one rare non-synonymous heterozygous variant F87I in an obese patient. Furthermore, we identified five different synonymous variants of which three (L53L, G326G and G370G) could solely be detected among obese children and two (P105P and A278A) were only present in lean individuals. L53L was identified among three different obese patients and was not present in the control population. MAQ analysis could not identify copy number variation in the NPY2R region in our population.
Conclusion: By performing in silico analysis, we determined that the F87I variant is probably damaging to the protein structure and might have a disease causing effect. Further functional testing will be necessary to fully understand the impact on NPY2R.
As we could not identify any CNV in the NPY2R region, structural variation in NPY2R is not likely to cause obesity.
Disclosure: This work was supported by the Institute for the Promotion of Innovation through Science and Technology in Flanders (PhD grant Grant for Strategic Basic Research with grant number 121250).
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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