title: Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression.
abstract: OBJECTIVE
  Receptor activator of nuclear factor-kappaB ligand/osteoprotegerin (RANKL/OPG) signaling system plays a crucial role in the regulation of bone resorption. Polymorphic variations in the genes may have an influence on gene expression and bone metabolism. In the present study, we aimed to investigate the influence of RANKL/OPG allelic variations on the in vivo human gene expression of five genes, bone mineral density (BMD), and fracture incidence in Hungarian postmenopausal women.
  
  
  METHODS
  Three hundred and sixty postmenopausal women (61.6+/-7.9 years) were genotyped. All together, five single nucleotide polymorphisms (SNPs) in the two genes have been investigated. In addition, bone samples from 17 examined subjects were acquired for gene expression studies. Bone densities and fracture data have also been collected.
  
  
  RESULTS
  All two SNPs in OPG gene and three SNPs in RANKL gene showed correlation with BMD. Haplotype analysis of these genes gave similar results. The 'CCT' haplotype of RANKL promoter region, which was associated with decreased BMD, exhibited a significantly upregulated expression of RANKL mRNA, while the other haplotypes of RANKL or OPG 15 genes did not. No correlation between genetic variations and fracture data was found.
  
  
  CONCLUSIONS
  We have demonstrated associations between RANKL and OPG haplotypes and BMD as well as between RANKL haplotypes and in vivo RANKL expression in a Hungarian postmenopausal population. Moreover, we have found a new RANKL haplotype associating with reduced BMD and increased in vivo RANKL expression in human bone tissue.
authors.affiliation: 1st Department of Internal Medicine, Semmelweis University, Korányi S u 2/a, Budapest H-1083, Hungary. takist@bel1.sote.hu
authors.forename: István
authors.initials: I
authors.lastname: Takács
authors.forename: Aron
authors.initials: A
authors.lastname: Lazáry
authors.forename: János P
authors.initials: JP
authors.lastname: Kósa
authors.forename: János
authors.initials: J
authors.lastname: Kiss
authors.forename: Bernadett
authors.initials: B
authors.lastname: Balla
authors.forename: Zsolt
authors.initials: Z
authors.lastname: Nagy
authors.forename: Krisztián
authors.initials: K
authors.lastname: Bácsi
authors.forename: Gabor
authors.initials: G
authors.lastname: Speer
authors.forename: Péter
authors.initials: P
authors.lastname: Lakatos
mesh_terms: D000368:Aged; D000483:Alleles; D015519:Bone Density / Q000235:genetics*; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology / Q000235:genetics; D015870:Gene Expression / Q000502:physiology; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D053244:Osteoprotegerin / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause; D053245:RANK Ligand / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D053244:Osteoprotegerin; D053245:RANK Ligand; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human