000063349 001__ 63349
000063349 005__ 20171129112118.0
000063349 0247_ $$2doi$$a10.1371/journal.pone.0070632
000063349 0248_ $$2sideral$$a82655
000063349 037__ $$aART-2013-82655
000063349 041__ $$aeng
000063349 100__ $$aGianfagna, F.
000063349 245__ $$aUnderstanding the Links among neuromedin U Gene, beta2-adrenoceptor Gene and Bone Health: An Observational Study in European Children
000063349 260__ $$c2013
000063349 5060_ $$aAccess copy available to the general public$$fUnrestricted
000063349 5203_ $$aNeuromedin 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, ¿¿=¿-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, ¿¿=¿-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 (¿¿=¿-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 ß-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.
000063349 536__ $$9info:eu-repo/grantAgreement/EUR/FP6/FOOD-016181
000063349 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000063349 590__ $$a3.534$$b2013
000063349 591__ $$aMULTIDISCIPLINARY SCIENCES$$b8 / 56 = 0.143$$c2013$$dQ1$$eT1
000063349 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000063349 700__ $$aCugino, D.
000063349 700__ $$aAhrens, W.
000063349 700__ $$aBailey, M.E.S.
000063349 700__ $$aBammann, K.
000063349 700__ $$aHerrmann, D.
000063349 700__ $$aKoni, A.C.
000063349 700__ $$aKourides, Y.
000063349 700__ $$aMarild, S.
000063349 700__ $$aMolnár, D.
000063349 700__ $$0(orcid)0000-0003-0454-653X$$aMoreno, L.A.$$uUniversidad de Zaragoza
000063349 700__ $$aPitsiladis, Y.P.
000063349 700__ $$aRusso, P.
000063349 700__ $$aSiani, A.
000063349 700__ $$aSieri, S.
000063349 700__ $$aSioen, I.
000063349 700__ $$aVeidebaum, T.
000063349 700__ $$aIacoviello, L.
000063349 7102_ $$11006$$2255$$aUniversidad de Zaragoza$$bDepartamento de Fisiatría y Enfermería$$cEnfermería
000063349 773__ $$g8, 8 (2013), e70632 [7 pp]$$pPLoS One$$tPLoS One$$x1932-6203
000063349 8564_ $$s172490$$uhttp://zaguan.unizar.es/record/63349/files/texto_completo.pdf$$yVersión publicada
000063349 8564_ $$s129631$$uhttp://zaguan.unizar.es/record/63349/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000063349 909CO $$ooai:zaguan.unizar.es:63349$$particulos$$pdriver
000063349 951__ $$a2017-11-28-13:52:31
000063349 980__ $$aARTICLE