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Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient
BACKGROUND: Melanocortin 4 receptor gene (MC4R) is an important regulator of food intake, body weight, and blood pressure. Mutations in MC4R are associated with the most common form of nonsyndromic monogenic obesity. MC4R variations have an autosomal co-/dominant model of inheritance. MC4R screening...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388727/ https://www.ncbi.nlm.nih.gov/pubmed/30863132 http://dx.doi.org/10.2147/DMSO.S189455 |
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author | da Fonseca, Ana Carolina Proença Abreu, Gabriella de Medeiros Zembrzuski, Verônica Marques Junior, Mario Campos Carneiro, João Regis Ivar Magno, Fernanda Cristina C Mattos Rosado, Eliane Lopes Nogueira Neto, José Firmino de Cabello, Giselda Maria Kalil Cabello, Pedro Hernán |
author_facet | da Fonseca, Ana Carolina Proença Abreu, Gabriella de Medeiros Zembrzuski, Verônica Marques Junior, Mario Campos Carneiro, João Regis Ivar Magno, Fernanda Cristina C Mattos Rosado, Eliane Lopes Nogueira Neto, José Firmino de Cabello, Giselda Maria Kalil Cabello, Pedro Hernán |
author_sort | da Fonseca, Ana Carolina Proença |
collection | PubMed |
description | BACKGROUND: Melanocortin 4 receptor gene (MC4R) is an important regulator of food intake, body weight, and blood pressure. Mutations in MC4R are associated with the most common form of nonsyndromic monogenic obesity. MC4R variations have an autosomal co-/dominant model of inheritance. MC4R screening could reveal individuals previously unrecognized with Mendelian form of obesity for further clinical management and genetic counseling. However, there are limited data regarding MC4R variants in patients with obesity from Brazil. The aim of this study was to screen the coding region of the MC4R gene in a Brazilian cohort of severely obese adults and to investigate the phenotype–genotype correlation within MC4R variant carriers. METHODS: This study comprised 157 adult participants, stratified according to the period of obesity onset. The first group included 97 patients with childhood-onset obesity (0–11 years) and the second group comprised 60 subjects with adolescence/youth-onset obesity (12–21 years). The entire coding region of MC4R gene was screened by Sanger sequencing. RESULTS: As a result, five previously described variants (Met1?, Ser36Thr, Val103Ile, Ile98=, and Phe202Leu) were identified. Met1? is a start lost codon variant, which affects the translation of MC4R. It was found in a female patient with childhood-onset obesity. We also compared the anthropometric and metabolic parameters between patients with MC4R missense variants (Ser36Thr, Val103Ile, and Phe202Leu) and noncarriers. Patients carrying MC4R variants had higher median of waist–hip ratio when compared to noncarriers (P=0.048). These missense variants were also associated with hypertension (P=0.014). Additionally, Val103Ile carriers had lower diastolic blood pressure and lower systolic blood pressure compared to noncarriers (P=0.020 and P=0.065, respectively). Val103Ile was also associated with hypertension (P=0.003). CONCLUSION: This study showed the prevalence of MC4R variants in a cohort of Brazilian adults with severe obesity. We also identified significant phenotype differences between carriers and noncarriers of missense variants in our sample, suggesting an important role of MC4R on body fat distribution and blood pressure. |
format | Online Article Text |
id | pubmed-6388727 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Dove Medical Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-63887272019-03-12 Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient da Fonseca, Ana Carolina Proença Abreu, Gabriella de Medeiros Zembrzuski, Verônica Marques Junior, Mario Campos Carneiro, João Regis Ivar Magno, Fernanda Cristina C Mattos Rosado, Eliane Lopes Nogueira Neto, José Firmino de Cabello, Giselda Maria Kalil Cabello, Pedro Hernán Diabetes Metab Syndr Obes Original Research BACKGROUND: Melanocortin 4 receptor gene (MC4R) is an important regulator of food intake, body weight, and blood pressure. Mutations in MC4R are associated with the most common form of nonsyndromic monogenic obesity. MC4R variations have an autosomal co-/dominant model of inheritance. MC4R screening could reveal individuals previously unrecognized with Mendelian form of obesity for further clinical management and genetic counseling. However, there are limited data regarding MC4R variants in patients with obesity from Brazil. The aim of this study was to screen the coding region of the MC4R gene in a Brazilian cohort of severely obese adults and to investigate the phenotype–genotype correlation within MC4R variant carriers. METHODS: This study comprised 157 adult participants, stratified according to the period of obesity onset. The first group included 97 patients with childhood-onset obesity (0–11 years) and the second group comprised 60 subjects with adolescence/youth-onset obesity (12–21 years). The entire coding region of MC4R gene was screened by Sanger sequencing. RESULTS: As a result, five previously described variants (Met1?, Ser36Thr, Val103Ile, Ile98=, and Phe202Leu) were identified. Met1? is a start lost codon variant, which affects the translation of MC4R. It was found in a female patient with childhood-onset obesity. We also compared the anthropometric and metabolic parameters between patients with MC4R missense variants (Ser36Thr, Val103Ile, and Phe202Leu) and noncarriers. Patients carrying MC4R variants had higher median of waist–hip ratio when compared to noncarriers (P=0.048). These missense variants were also associated with hypertension (P=0.014). Additionally, Val103Ile carriers had lower diastolic blood pressure and lower systolic blood pressure compared to noncarriers (P=0.020 and P=0.065, respectively). Val103Ile was also associated with hypertension (P=0.003). CONCLUSION: This study showed the prevalence of MC4R variants in a cohort of Brazilian adults with severe obesity. We also identified significant phenotype differences between carriers and noncarriers of missense variants in our sample, suggesting an important role of MC4R on body fat distribution and blood pressure. Dove Medical Press 2019-02-21 /pmc/articles/PMC6388727/ /pubmed/30863132 http://dx.doi.org/10.2147/DMSO.S189455 Text en © 2019 Fonseca et al. This work is published and licensed by Dove Medical Press Limited The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. |
spellingShingle | Original Research da Fonseca, Ana Carolina Proença Abreu, Gabriella de Medeiros Zembrzuski, Verônica Marques Junior, Mario Campos Carneiro, João Regis Ivar Magno, Fernanda Cristina C Mattos Rosado, Eliane Lopes Nogueira Neto, José Firmino de Cabello, Giselda Maria Kalil Cabello, Pedro Hernán Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient |
title | Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient |
title_full | Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient |
title_fullStr | Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient |
title_full_unstemmed | Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient |
title_short | Identification of the MC4R start lost mutation in a morbidly obese Brazilian patient |
title_sort | identification of the mc4r start lost mutation in a morbidly obese brazilian patient |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6388727/ https://www.ncbi.nlm.nih.gov/pubmed/30863132 http://dx.doi.org/10.2147/DMSO.S189455 |
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