Advanced search
1 file | 224.74 KB Add to list

Understanding the links among neuromedin U gene, beta2-adrenoceptor gene and bone health : an observational study in European children

(2013) PLOS ONE. 8(8).
Author
Organization
Abstract
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, Delta = -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, Delta = -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 (Delta = -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 beta-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.
Keywords
QUANTITATIVE ULTRASOUND, CALCANEUS ULTRASOUND, BIOLOGICAL MARKERS, CHILDHOOD OBESITY, MINERAL DENSITY, OS CALCIS, IDEFICS, ADOLESCENTS, X-RAY ABSORPTIOMETRY, GENOME-WIDE ASSOCIATION

Downloads

  • Gianfagna 2013 genes and bone health.pdf
    • full text
    • |
    • open access
    • |
    • PDF
    • |
    • 224.74 KB

Citation

Please use this url to cite or link to this publication:

MLA
Gianfagna, Francesco, Daniela Cugino, Wolfgang Ahrens, et al. “Understanding the Links Among Neuromedin U Gene, Beta2-adrenoceptor Gene and Bone Health : an Observational Study in European Children.” PLOS ONE 8.8 (2013): n. pag. Print.
APA
Gianfagna, F., Cugino, D., Ahrens, W., Bailey, M. E., Bammann, K., Herrmann, D., Koni, A. C., et al. (2013). Understanding the links among neuromedin U gene, beta2-adrenoceptor gene and bone health : an observational study in European children. PLOS ONE, 8(8).
Chicago author-date
Gianfagna, Francesco, Daniela Cugino, Wolfgang Ahrens, Mark ES Bailey, Karin Bammann, Diana Herrmann, Anna C Koni, et al. 2013. “Understanding the Links Among Neuromedin U Gene, Beta2-adrenoceptor Gene and Bone Health : an Observational Study in European Children.” Plos One 8 (8).
Chicago author-date (all authors)
Gianfagna, Francesco, Daniela Cugino, Wolfgang Ahrens, Mark ES Bailey, Karin Bammann, Diana Herrmann, Anna C Koni, Yiannis Kourides, Staffan Marild, Dénes Molnár, Luis A Moreno, Yannis P Pitsiladis, Paola Russo, Alfonso Siani, Sabina Sieri, Isabelle Sioen, Toomas Veidebaum, and Licia Iacoviello. 2013. “Understanding the Links Among Neuromedin U Gene, Beta2-adrenoceptor Gene and Bone Health : an Observational Study in European Children.” Plos One 8 (8).
Vancouver
1.
Gianfagna F, Cugino D, Ahrens W, Bailey ME, Bammann K, Herrmann D, et al. Understanding the links among neuromedin U gene, beta2-adrenoceptor gene and bone health : an observational study in European children. PLOS ONE. 2013;8(8).
IEEE
[1]
F. Gianfagna et al., “Understanding the links among neuromedin U gene, beta2-adrenoceptor gene and bone health : an observational study in European children,” PLOS ONE, vol. 8, no. 8, 2013.
@article{4374202,
  abstract     = {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, Delta = -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, Delta = -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 (Delta = -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 beta-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.},
  articleno    = {e70632},
  author       = {Gianfagna, Francesco and Cugino, Daniela and Ahrens, Wolfgang and Bailey, Mark ES and Bammann, Karin and Herrmann, Diana and Koni, Anna C and Kourides, Yiannis and Marild, Staffan and Molnár, Dénes and Moreno, Luis A and Pitsiladis, Yannis P and Russo, Paola and Siani, Alfonso and Sieri, Sabina and Sioen, Isabelle and Veidebaum, Toomas and Iacoviello, Licia},
  issn         = {1932-6203},
  journal      = {PLOS ONE},
  keywords     = {QUANTITATIVE ULTRASOUND,CALCANEUS ULTRASOUND,BIOLOGICAL MARKERS,CHILDHOOD OBESITY,MINERAL DENSITY,OS CALCIS,IDEFICS,ADOLESCENTS,X-RAY ABSORPTIOMETRY,GENOME-WIDE ASSOCIATION},
  language     = {eng},
  number       = {8},
  pages        = {7},
  title        = {Understanding the links among neuromedin U gene, beta2-adrenoceptor gene and bone health : an observational study in European children},
  url          = {http://dx.doi.org/10.1371/journal.pone.0070632},
  volume       = {8},
  year         = {2013},
}

Altmetric
View in Altmetric
Web of Science
Times cited: