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Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children

Neuromedin U, encoded by the NMU gene, is a hypothalamic neuropeptide that regulates both energy metabolism and bone mass. The beta-2 adrenergic receptor, encoded by the ADRB2 gene, mediates several effects of catecholamine hormones and neurotransmitters in bone. We investigated whether NMU single n...

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Autores principales: Gianfagna, Francesco, Cugino, Daniela, Ahrens, Wolfgang, Bailey, Mark E. S., Bammann, Karin, Herrmann, Diana, Koni, Anna C., Kourides, Yiannis, Marild, Staffan, Molnár, Dénes, Moreno, Luis A., Pitsiladis, Yannis P., Russo, Paola, Siani, Alfonso, Sieri, Sabina, Sioen, Isabelle, Veidebaum, Toomas, Iacoviello, Licia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731254/
https://www.ncbi.nlm.nih.gov/pubmed/23936460
http://dx.doi.org/10.1371/journal.pone.0070632
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author Gianfagna, Francesco
Cugino, Daniela
Ahrens, Wolfgang
Bailey, Mark E. S.
Bammann, Karin
Herrmann, Diana
Koni, Anna C.
Kourides, Yiannis
Marild, Staffan
Molnár, Dénes
Moreno, Luis A.
Pitsiladis, Yannis P.
Russo, Paola
Siani, Alfonso
Sieri, Sabina
Sioen, Isabelle
Veidebaum, Toomas
Iacoviello, Licia
author_facet Gianfagna, Francesco
Cugino, Daniela
Ahrens, Wolfgang
Bailey, Mark E. S.
Bammann, Karin
Herrmann, Diana
Koni, Anna C.
Kourides, Yiannis
Marild, Staffan
Molnár, Dénes
Moreno, Luis A.
Pitsiladis, Yannis P.
Russo, Paola
Siani, Alfonso
Sieri, Sabina
Sioen, Isabelle
Veidebaum, Toomas
Iacoviello, Licia
author_sort Gianfagna, Francesco
collection PubMed
description Neuromedin U, encoded by the NMU gene, is a hypothalamic neuropeptide that regulates both energy metabolism and bone mass. The beta-2 adrenergic receptor, encoded by the ADRB2 gene, mediates several effects of catecholamine hormones and neurotransmitters in bone. We investigated whether NMU single nucleotide polymorphisms (SNPs) and haplotypes, as well as functional ADRB2 SNPs, are associated with bone stiffness in children from the IDEFICS cohort, also evaluating whether NMU and ADRB2 interact to affect this trait. A sample of 2,274 subjects (52.5% boys, age 6.2±1.8 years) from eight European countries, having data on calcaneus bone stiffness index (SI, mean of both feet) and genotyping (NMU gene: rs6827359, rs12500837, rs9999653; ADRB2 gene: rs1042713, rs1042714), was studied. After false discovery rate adjustment, SI was significantly associated with all NMU SNPs. rs6827359 CC homozygotes showed the strongest association (recessive model, Δ = −1.8, p = 0.006). Among the five retrieved haplotypes with frequencies higher than 1% (range 2.0–43.9%), the CCT haplotype (frequency = 39.7%) was associated with lower SI values (dominant model, Δ = −1.0, p = 0.04) as compared to the most prevalent haplotype. A non-significant decrease in SI was observed in in ADRB2 rs1042713 GG homozygotes, while subjects carrying SI-lowering genotypes at both SNPs (frequency = 8.4%) showed much lower SI than non-carriers (Δ = −3.9, p<0.0001; p for interaction = 0.025). The association was more evident in preschool girls, in whom SI showed a curvilinear trend across ages. In subgroup analyses, rs9999653 CC NMU or both GG ADRB2 genotypes were associated with either lower serum calcium or β-CrossLaps levels (p = 0.01). This study in European children shows, for the first time in humans, a role for NMU gene through interaction with ADRB2 gene in bone strength regulation, more evident in preschool girls.
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spelling pubmed-37312542013-08-09 Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children Gianfagna, Francesco Cugino, Daniela Ahrens, Wolfgang Bailey, Mark E. S. Bammann, Karin Herrmann, Diana Koni, Anna C. Kourides, Yiannis Marild, Staffan Molnár, Dénes Moreno, Luis A. Pitsiladis, Yannis P. Russo, Paola Siani, Alfonso Sieri, Sabina Sioen, Isabelle Veidebaum, Toomas Iacoviello, Licia PLoS One Research Article Neuromedin U, encoded by the NMU gene, is a hypothalamic neuropeptide that regulates both energy metabolism and bone mass. The beta-2 adrenergic receptor, encoded by the ADRB2 gene, mediates several effects of catecholamine hormones and neurotransmitters in bone. We investigated whether NMU single nucleotide polymorphisms (SNPs) and haplotypes, as well as functional ADRB2 SNPs, are associated with bone stiffness in children from the IDEFICS cohort, also evaluating whether NMU and ADRB2 interact to affect this trait. A sample of 2,274 subjects (52.5% boys, age 6.2±1.8 years) from eight European countries, having data on calcaneus bone stiffness index (SI, mean of both feet) and genotyping (NMU gene: rs6827359, rs12500837, rs9999653; ADRB2 gene: rs1042713, rs1042714), was studied. After false discovery rate adjustment, SI was significantly associated with all NMU SNPs. rs6827359 CC homozygotes showed the strongest association (recessive model, Δ = −1.8, p = 0.006). Among the five retrieved haplotypes with frequencies higher than 1% (range 2.0–43.9%), the CCT haplotype (frequency = 39.7%) was associated with lower SI values (dominant model, Δ = −1.0, p = 0.04) as compared to the most prevalent haplotype. A non-significant decrease in SI was observed in in ADRB2 rs1042713 GG homozygotes, while subjects carrying SI-lowering genotypes at both SNPs (frequency = 8.4%) showed much lower SI than non-carriers (Δ = −3.9, p<0.0001; p for interaction = 0.025). The association was more evident in preschool girls, in whom SI showed a curvilinear trend across ages. In subgroup analyses, rs9999653 CC NMU or both GG ADRB2 genotypes were associated with either lower serum calcium or β-CrossLaps levels (p = 0.01). This study in European children shows, for the first time in humans, a role for NMU gene through interaction with ADRB2 gene in bone strength regulation, more evident in preschool girls. Public Library of Science 2013-08-01 /pmc/articles/PMC3731254/ /pubmed/23936460 http://dx.doi.org/10.1371/journal.pone.0070632 Text en © 2013 Gianfagna et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Gianfagna, Francesco
Cugino, Daniela
Ahrens, Wolfgang
Bailey, Mark E. S.
Bammann, Karin
Herrmann, Diana
Koni, Anna C.
Kourides, Yiannis
Marild, Staffan
Molnár, Dénes
Moreno, Luis A.
Pitsiladis, Yannis P.
Russo, Paola
Siani, Alfonso
Sieri, Sabina
Sioen, Isabelle
Veidebaum, Toomas
Iacoviello, Licia
Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children
title Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children
title_full Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children
title_fullStr Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children
title_full_unstemmed Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children
title_short Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children
title_sort understanding the links among neuromedin u gene, beta2-adrenoceptor gene and bone health: an observational study in european children
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3731254/
https://www.ncbi.nlm.nih.gov/pubmed/23936460
http://dx.doi.org/10.1371/journal.pone.0070632
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