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

Francesco Gianfagna, Daniela Cugino, Wolfgang Ahrens, Mark E S 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, Licia Iacoviello

Research output: Contribution to journalArticle

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, 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

Original languageEnglish
Article numbere70632
JournalPLoS One
Volume8
Issue number8
DOIs
Publication statusPublished - Aug 1 2013

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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    Gianfagna, F., Cugino, D., Ahrens, W., Bailey, M. E. S., Bammann, K., Herrmann, D., Koni, A. C., Kourides, Y., Marild, S., Molnár, D., Moreno, L. A., Pitsiladis, Y. P., Russo, P., Siani, A., Sieri, S., Sioen, I., Veidebaum, T., & Iacoviello, L. (2013). Understanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children. PLoS One, 8(8), [e70632]. https://doi.org/10.1371/journal.pone.0070632