High Prevalence of Rare Monogenic Forms of Obesity in Obese Guadeloupean Afro-Caribbean Children.

Autor:	Foucan L; Research Team on Cardiometabolic Risk, University of Antilles, Pointe-à-Pitre, Guadeloupe, France.; Department of Public Health, University Hospital, Pointe-à-Pitre, Guadeloupe, France., Larifla L; Research Team on Cardiometabolic Risk, University of Antilles, Pointe-à-Pitre, Guadeloupe, France.; Cardiology Unit, University Hospital, Pointe-à-Pitre, Guadeloupe, France., Durand E; CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France., Rambhojan C; Research Team on Cardiometabolic Risk, University of Antilles, Pointe-à-Pitre, Guadeloupe, France., Armand C; Research Team on Cardiometabolic Risk, University of Antilles, Pointe-à-Pitre, Guadeloupe, France.; Department of Public Health, University Hospital, Pointe-à-Pitre, Guadeloupe, France., Michel CT; Cardiology Unit, University Hospital, Pointe-à-Pitre, Guadeloupe, France., Billy R; Cardiology Unit, University Hospital, Pointe-à-Pitre, Guadeloupe, France., Dhennin V; CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France., De Graeve F; CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France., Rabearivelo I; CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France., Sand O; CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France., Lacorte JM; Department of Endocrine and Oncological Biochemistry, University Hospitals of Pitié-Salpétrière‒Charles Foix, Paris, France.; Inserm, Research Institute of Cardiovascular Disease, Metabolism and Nutrition, Paris, France., Froguel P; CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France.; Department of Genomics of Common Disease, Imperial College London, London, United Kingdom., Bonnefond A; CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France.; Department of Genomics of Common Disease, Imperial College London, London, United Kingdom.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2018 Feb 01; Vol. 103 (2), pp. 539-545.
DOI:	10.1210/jc.2017-01956
Abstrakt:	Context: The population of Guadeloupe Island exhibits a high prevalence of obesity. Objective: We aimed to investigate whether rare genetic mutations in genes involved in monogenic obesity (or diabetes) might be causal in this population of Afro-Caribbean ancestry. Design and Setting: This was a secondary analysis of a study on obesity conducted in schoolchildren from Guadeloupe in 2013 that aimed to assess changes in children's profiles after a lifestyle intervention program. Through next-generation sequencing, we sequenced coding regions of 59 genes involved in monogenic obesity or diabetes in participants from this study. Participants and Interventions: A total of 25 obese schoolchildren from Guadeloupe were screened for rare mutations (nonsynonymous, splice-site, or insertion/deletion) in 59 genes. Main Outcome Measures: Correlation between phenotypes and mutations of interest. Results: We detected five rare heterozygous mutations in five different children with obesity: MC4R p.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations that were pathogenic; SIM1 p.Ser343Pro and SH2B1 p.Pro90His mutations that were likely pathogenic; and NTRK2 p.Leu140Phe that was of uncertain significance. In parallel, we identified seven carriers of mutations in ABCC8 (p.Lys1521Asn and p.Ala625Val) or KCNJ11 (p.Val13Met and p.Val151Met) that were of uncertain significance. Conclusions: We were able to detect pathogenic or likely pathogenic mutations linked to severe obesity in >15% of this population, which is much higher than what we observed in Europeans (∼5%). (Copyright © 2017 Endocrine Society)
Databáze:	MEDLINE
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