Lydia Foucan1,2, Laurent Larifla1,3, Emmanuelle Durand4, Christine Rambhojan1, Christophe Armand1,2, Carl-Thony Michel3, Rachel Billy3, Véronique Dhennin4, Franck De Graeve4, Iandry Rabearivelo4, Olivier Sand4, Jean-Marc Lacorte5,6, Philippe Froguel4,7, Amélie Bonnefond4,7. 1. Research Team on Cardiometabolic Risk, University of Antilles, Pointe-à-Pitre, Guadeloupe, France. 2. Department of Public Health, University Hospital, Pointe-à-Pitre, Guadeloupe, France. 3. Cardiology Unit, University Hospital, Pointe-à-Pitre, Guadeloupe, France. 4. CNRS, European Genomic Institute for Diabetes, Institut Pasteur de Lille, University of Lille, Lille, France. 5. Department of Endocrine and Oncological Biochemistry, University Hospitals of Pitié-Salpétrière‒Charles Foix, Paris, France. 6. Inserm, Research Institute of Cardiovascular Disease, Metabolism and Nutrition, Paris, France. 7. Department of Genomics of Common Disease, Imperial College London, London, United Kingdom.
Abstract
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%).
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: MC4Rp.Ile301Thr and SIM1 p.Val326Thrfs*43 mutations that were pathogenic; SIM1 p.Ser343Pro and SH2B1p.Pro90His mutations that were likely pathogenic; and NTRK2p.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%).
Authors: Maria Caterina De Rosa; Alessandra Chesi; Shana McCormack; Justin Zhou; Benjamin Weaver; Molly McDonald; Sinead Christensen; Kalle Liimatta; Michael Rosenbaum; Hakon Hakonarson; Claudia A Doege; Struan F A Grant; Joel N Hirschhorn; Vidhu V Thaker Journal: J Clin Endocrinol Metab Date: 2019-07-01 Impact factor: 5.958
Authors: Mellody I Cooiman; Lotte Kleinendorst; Bert van der Zwaag; Ignace M C Janssen; Frits J Berends; Mieke M van Haelst Journal: Mol Genet Genomic Med Date: 2019-05-04 Impact factor: 2.183