title: RANKL/RANK/OPG Polymorphisms and Heel Quantitative Ultrasound in Young Adults.
abstract: The receptor activator of the nuclear factor-kappa B ligand (RANKL), the receptor activator of nuclear factor-kappa B (RANK), and the osteoprotegerin (OPG) signaling pathway play an important role in the regulation of bone remodeling and osteoclast differentiation. Quantitative ultrasound (QUS) is a relatively recent and noninvasive method providing structural information on microstructure, bone elasticity, and connectivity. However, in contrast to bone mineral density measurements, the possible association of the RANKL/RANK/OPG pathway with heel QUS has not been analyzed.
  
  
  
  The aim of this study was to assess, for the first time, the contribution of the RANKL/RANK/OPG pathway genes in the genetic background of heel QUS parameters.
  
  
  
  Ten single-nucleotide polymorphisms (SNPs) of RANKL (rs9594759, rs12585014, rs7988338, rs2148073), RANK (rs1805034, rs12458117, rs3018362), and OPG (rs4355801, rs3102735, rs2073618) were selected as genetic markers and genotyped using Open Array technology in 575 self-reported Caucasian individuals aged 18-25. Bone mass in the right calcaneus was estimated with QUS to obtain the broadband ultrasound attenuation (BUA) measurement (dB/MHz). Linear regression analyses were performed to test the possible association between the SNPs and BUA.
  
  
  
  Linear regression analysis of all the tested SNPs revealed no significant association with the BUA parameter after adjusting for age, gender, weight, height, physical activity, and calcium intake. The lowest p-value was observed for the rs9594759 RANKL polymorphism and heel QUS (p = .06; b* = -.075, 95% CI [-0.960, 0.028]).
  
  
  
  Our results suggest that the polymorphism of the RANKL, RANK, and OPG genes does not make a significant genetic contribution to heel ultrasound measurements in a population of young Caucasian adults. Further studies replicating the results in independent populations are needed to support these initial findings.
authors.affiliation: María Correa-Rodríguez, RN, is doctoral student; Jacqueline Schmidt Rio-Valle, PhD, is Professor; and Blanca Rueda-Medina, PhD, is Professor, Department of Nursing, Faculty of Health Sciences, University of Granada, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Correa-Rodríguez
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schmidt-RioValle
authors.forename: Blanca
authors.initials: B
authors.lastname: Rueda-Medina
mesh_terms: D000328:Adult; D016723:Bone Remodeling / Q000235:genetics*; D002111:Calcaneus / Q000000981:diagnostic imaging*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D016014:Linear Models; D008297:Male; D053244:Osteoprotegerin / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D053244:Osteoprotegerin; D053246:Receptor Activator of Nuclear Factor-kappa B; C505686:TNFRSF11A protein, human; C506030:TNFRSF11B protein, human