A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity
Ana Carolina Proença da Fonseca,1,2 Gabriella de Medeiros Abreu,2 Lohanna Palhinha,1 Verônica Marques Zembrzuski,2 Mario Campos Junior,2 João Regis Ivar Carneiro,3 José Firmino Nogueira Neto,4 Fernanda Cristina C Mattos Magno,5 Eliane Lopes Rosado,5 Clariss...
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2021
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bdnf severe obesity rare mutation early-onset obesity metabolic syndrome Specialties of internal medicine RC581-951 |
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bdnf severe obesity rare mutation early-onset obesity metabolic syndrome Specialties of internal medicine RC581-951 da Fonseca ACP Abreu GM Palhinha L Zembrzuski VM Campos Junior M Carneiro JRI Nogueira Neto JF Magno FCCM Rosado EL Maya-Monteiro CM Cabello GMK Cabello PH Bozza PT A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity |
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Ana Carolina Proença da Fonseca,1,2 Gabriella de Medeiros Abreu,2 Lohanna Palhinha,1 Verônica Marques Zembrzuski,2 Mario Campos Junior,2 João Regis Ivar Carneiro,3 José Firmino Nogueira Neto,4 Fernanda Cristina C Mattos Magno,5 Eliane Lopes Rosado,5 Clarissa Menezes Maya-Monteiro,1 Giselda Maria Kalil de Cabello,2 Pedro Hernán Cabello,2,6 Patricia Torres Bozza1 1Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 2Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 3Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 4Department of Pathology and Laboratory, Rio de Janeiro State University, Rio de Janeiro, Brazil; 5Institute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 6Human Genetics Laboratory, Grande Rio University, Rio de Janeiro, BrazilCorrespondence: Ana Carolina Proença da FonsecaHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 4365 Brasil Avenue, Leônidas Deane Building – Office 611/615, Rio de Janeiro, RJ 21040-360, BrazilTel +552138658192Fax +552138658239Email ana.proenca@ioc.fiocruz.brBackground: Brain-derived neurotrophic factor (BDNF) is a pro-survival factor in the brain that also regulates energy balance. BDNF loss-of-function point mutations are responsible for haploinsufficiency, causing severe early-onset obesity. Up to date, only a few studies have sequenced this gene to search for rare mutations related to obesity. In this study, we aimed to investigate the prevalence of BDNF variants in a cohort of adults with severe obesity from Brazil.Material and Methods: This study comprised 201 adults with severe obesity (BMI ≥ 35.0 kg/m2) with onset during childhood- or adolescence/youth. As controls, 73 subjects with normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2) were selected. The exclusion criteria were pregnancy, lactation, the use of medication to lose or gain weight, and the presence of symptoms suggestive of syndromic obesity (only for the case group). The coding region of the BDNF gene was screened by Sanger sequencing. Demographic, anthropometric, and blood pressure parameters were obtained from the participants as well as serum hormone and cytokines concentrations and biochemical values.Results: As a result, three missense variants [p.(Thr2Ile), p.(Val66Met), and p.(Arg209Gln)] and four synonymous variants (p.Leu107=, p.Thr149=, p.Ala150=, and p.Ser213=) were identified. The p.(Arg209Gln) was predicted as pathogenic by all in silico algorithms used and was not observed in the control group. The individuals carrying the p.(Val66Met) mutated allele had higher waist circumference, HDL-cholesterol and MCP1 levels, and reduced risk of developing metabolic syndrome.Conclusion: We observed that the common BDNF p.(Val66Met) variant has influenced waist circumference, HDL-cholesterol, and MCP1 levels. This polymorphism has also a protective effect on metabolic syndrome susceptibility. Additionally, we described for the first time a rare potentially pathogenic BDNF variant in a Brazilian patient with severe obesity and childhood-onset.Keywords: BDNF, severe obesity, rare mutation, early-onset obesity, metabolic syndrome |
| format |
article |
| author |
da Fonseca ACP Abreu GM Palhinha L Zembrzuski VM Campos Junior M Carneiro JRI Nogueira Neto JF Magno FCCM Rosado EL Maya-Monteiro CM Cabello GMK Cabello PH Bozza PT |
| author_facet |
da Fonseca ACP Abreu GM Palhinha L Zembrzuski VM Campos Junior M Carneiro JRI Nogueira Neto JF Magno FCCM Rosado EL Maya-Monteiro CM Cabello GMK Cabello PH Bozza PT |
| author_sort |
da Fonseca ACP |
| title |
A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity |
| title_short |
A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity |
| title_full |
A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity |
| title_fullStr |
A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity |
| title_full_unstemmed |
A Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity |
| title_sort |
rare potential pathogenic variant in the bdnf gene is found in a brazilian patient with severe childhood-onset obesity |
| publisher |
Dove Medical Press |
| publishDate |
2021 |
| url |
https://doaj.org/article/73926877d6b64818a451f74a1cd8fcab |
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oai:doaj.org-article:73926877d6b64818a451f74a1cd8fcab2021-12-02T10:40:53ZA Rare Potential Pathogenic Variant in the BDNF Gene is Found in a Brazilian Patient with Severe Childhood-Onset Obesity1178-7007https://doaj.org/article/73926877d6b64818a451f74a1cd8fcab2021-01-01T00:00:00Zhttps://www.dovepress.com/a-rare-potential-pathogenic-variant-in-the-bdnf-gene-is-found-in-a-bra-peer-reviewed-article-DMSOhttps://doaj.org/toc/1178-7007Ana Carolina Proença da Fonseca,1,2 Gabriella de Medeiros Abreu,2 Lohanna Palhinha,1 Verônica Marques Zembrzuski,2 Mario Campos Junior,2 João Regis Ivar Carneiro,3 José Firmino Nogueira Neto,4 Fernanda Cristina C Mattos Magno,5 Eliane Lopes Rosado,5 Clarissa Menezes Maya-Monteiro,1 Giselda Maria Kalil de Cabello,2 Pedro Hernán Cabello,2,6 Patricia Torres Bozza1 1Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 2Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil; 3Clementino Fraga Filho University Hospital, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 4Department of Pathology and Laboratory, Rio de Janeiro State University, Rio de Janeiro, Brazil; 5Institute of Nutrition Josué de Castro, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; 6Human Genetics Laboratory, Grande Rio University, Rio de Janeiro, BrazilCorrespondence: Ana Carolina Proença da FonsecaHuman Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, 4365 Brasil Avenue, Leônidas Deane Building – Office 611/615, Rio de Janeiro, RJ 21040-360, BrazilTel +552138658192Fax +552138658239Email ana.proenca@ioc.fiocruz.brBackground: Brain-derived neurotrophic factor (BDNF) is a pro-survival factor in the brain that also regulates energy balance. BDNF loss-of-function point mutations are responsible for haploinsufficiency, causing severe early-onset obesity. Up to date, only a few studies have sequenced this gene to search for rare mutations related to obesity. In this study, we aimed to investigate the prevalence of BDNF variants in a cohort of adults with severe obesity from Brazil.Material and Methods: This study comprised 201 adults with severe obesity (BMI ≥ 35.0 kg/m2) with onset during childhood- or adolescence/youth. As controls, 73 subjects with normal weight (18.5 ≤ BMI ≤ 24.9 kg/m2) were selected. The exclusion criteria were pregnancy, lactation, the use of medication to lose or gain weight, and the presence of symptoms suggestive of syndromic obesity (only for the case group). The coding region of the BDNF gene was screened by Sanger sequencing. Demographic, anthropometric, and blood pressure parameters were obtained from the participants as well as serum hormone and cytokines concentrations and biochemical values.Results: As a result, three missense variants [p.(Thr2Ile), p.(Val66Met), and p.(Arg209Gln)] and four synonymous variants (p.Leu107=, p.Thr149=, p.Ala150=, and p.Ser213=) were identified. The p.(Arg209Gln) was predicted as pathogenic by all in silico algorithms used and was not observed in the control group. The individuals carrying the p.(Val66Met) mutated allele had higher waist circumference, HDL-cholesterol and MCP1 levels, and reduced risk of developing metabolic syndrome.Conclusion: We observed that the common BDNF p.(Val66Met) variant has influenced waist circumference, HDL-cholesterol, and MCP1 levels. This polymorphism has also a protective effect on metabolic syndrome susceptibility. Additionally, we described for the first time a rare potentially pathogenic BDNF variant in a Brazilian patient with severe obesity and childhood-onset.Keywords: BDNF, severe obesity, rare mutation, early-onset obesity, metabolic syndromeda Fonseca ACPAbreu GMPalhinha LZembrzuski VMCampos Junior MCarneiro JRINogueira Neto JFMagno FCCMRosado ELMaya-Monteiro CMCabello GMKCabello PHBozza PTDove Medical Pressarticlebdnfsevere obesityrare mutationearly-onset obesitymetabolic syndromeSpecialties of internal medicineRC581-951ENDiabetes, Metabolic Syndrome and Obesity: Targets and Therapy, Vol Volume 14, Pp 11-22 (2021) |