Cargando…
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...
Autores principales: | , , , , , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1782279131517419520 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3731254 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT gianfagnafrancesco understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT cuginodaniela understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT ahrenswolfgang understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT baileymarkes understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT bammannkarin understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT herrmanndiana understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT koniannac understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT kouridesyiannis understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT marildstaffan understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT molnardenes understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT morenoluisa understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT pitsiladisyannisp understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT russopaola understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT sianialfonso understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT sierisabina understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT sioenisabelle understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT veidebaumtoomas understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT iacoviellolicia understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren AT understandingthelinksamongneuromedinugenebeta2adrenoceptorgeneandbonehealthanobservationalstudyineuropeanchildren |