Polymorphisms in the endothelial nitric oxide synthase gene and bone density/ultrasound and geometry in humans

K. Cho, S. Demissie, J. Dupuis, L. A. Cupples, S. Kathiresan, T. J. Beck, D. Karasik, D. P. Kiel

Research output: Contribution to journalArticle

Abstract

Nitric oxide (NO), produced by endothelial cells, is a signaling molecule synthesized from l-arginine by nitric oxide synthases (NOS). NO is known to reduce the ratio of receptor activator of nuclear factor KappaB (RANKL)/osteoprotegerin (OPG), leading to decreased osteoclastogenesis and a reduction in bone resorption. Endothelial nitric oxide synthase (eNOS or NOS3) is the predominant constitutive isoform of nitric NOS within bone. Recently, a NOS3 polymorphism, Glu298Asp, previously implicated in osteoporosis, failed to demonstrate an association with bone mineral density (BMD), although there was some indication of an association with selected geometry indices. Since a single polymorphism does not capture all of the potential variants in a given gene, we investigated a broader coverage of the NOS3 gene with bone density/ultrasound and geometry indices in a sample of unrelated individuals from the Framingham Offspring Study. Our results indicated that the Glu298Asp polymorphism was not associated with BMD but suggested some haplotype-based associations in the linkage disequilibrium (LD) region that included the Glu298Asp polymorphism with several geometry indices. Although our findings exhibited several associations with selected bone density/ultrasound and geometry indices, the nominally significant associations are regarded as primarily hypothesis generating and suggest that replication in other samples is needed. Thus, NOS3 genetic variation does not appear to be a major contributor to adult bone density/ultrasound and geometry in our sample.

Original languageEnglish (US)
Pages (from-to)53-60
Number of pages8
JournalBone
Volume42
Issue number1
DOIs
StatePublished - Jan 2008

Fingerprint

Nitric Oxide Synthase Type III
Bone Density
Genes
Nitric Oxide Synthase
Receptor Activator of Nuclear Factor-kappa B
Nitric Oxide
Osteoprotegerin
Linkage Disequilibrium
Bone Resorption
Osteogenesis
Haplotypes
Osteoporosis
Arginine
Protein Isoforms
Endothelial Cells
Bone and Bones

Keywords

  • Bone density/ultrasound
  • Bone geometry
  • Genetic polymorphisms
  • Nitric oxide synthase
  • Osteoporosis

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Cho, K., Demissie, S., Dupuis, J., Cupples, L. A., Kathiresan, S., Beck, T. J., ... Kiel, D. P. (2008). Polymorphisms in the endothelial nitric oxide synthase gene and bone density/ultrasound and geometry in humans. Bone, 42(1), 53-60. https://doi.org/10.1016/j.bone.2007.09.051

Polymorphisms in the endothelial nitric oxide synthase gene and bone density/ultrasound and geometry in humans. / Cho, K.; Demissie, S.; Dupuis, J.; Cupples, L. A.; Kathiresan, S.; Beck, T. J.; Karasik, D.; Kiel, D. P.

In: Bone, Vol. 42, No. 1, 01.2008, p. 53-60.

Research output: Contribution to journalArticle

Cho, K, Demissie, S, Dupuis, J, Cupples, LA, Kathiresan, S, Beck, TJ, Karasik, D & Kiel, DP 2008, 'Polymorphisms in the endothelial nitric oxide synthase gene and bone density/ultrasound and geometry in humans', Bone, vol. 42, no. 1, pp. 53-60. https://doi.org/10.1016/j.bone.2007.09.051
Cho, K. ; Demissie, S. ; Dupuis, J. ; Cupples, L. A. ; Kathiresan, S. ; Beck, T. J. ; Karasik, D. ; Kiel, D. P. / Polymorphisms in the endothelial nitric oxide synthase gene and bone density/ultrasound and geometry in humans. In: Bone. 2008 ; Vol. 42, No. 1. pp. 53-60.
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