Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression

I. Takács, Áron Lazáry, J. Kósa, János Kiss, Bernadett Balla, Zsolt Nagy, Krisztián Bácsi, G. Speer, P. Lakatos

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Objective: Receptor activator of nuclear factor-kB 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)423-431
Number of pages9
JournalEuropean Journal of Endocrinology
Volume162
Issue number2
DOIs
Publication statusPublished - Feb 1 2010

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RANK Ligand
Cytoplasmic and Nuclear Receptors
Bone Density
Haplotypes
Gene Expression
Genes
Single Nucleotide Polymorphism
Bone Fractures
Bone and Bones
Bone Resorption
Genetic Promoter Regions
Messenger RNA
Incidence

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression. / Takács, I.; Lazáry, Áron; Kósa, J.; Kiss, János; Balla, Bernadett; Nagy, Zsolt; Bácsi, Krisztián; Speer, G.; Lakatos, P.

In: European Journal of Endocrinology, Vol. 162, No. 2, 01.02.2010, p. 423-431.

Research output: Contribution to journalArticle

Takács, I. ; Lazáry, Áron ; Kósa, J. ; Kiss, János ; Balla, Bernadett ; Nagy, Zsolt ; Bácsi, Krisztián ; Speer, G. ; Lakatos, P. / Allelic variations of RANKL/OPG signaling system are related to bone mineral density and in vivo gene expression. In: European Journal of Endocrinology. 2010 ; Vol. 162, No. 2. pp. 423-431.
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AU - Balla, Bernadett

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