Calcified Tissue International

, Volume 77, Issue 3, pp 145–151

Klotho Gene Polymorphisms are Associated with Osteocalcin Levels but not Bone Density of Aged Postmenopausal Women

Authors

  • B.H. Mullin
    • Dept.of Endocrinology and DiabetesSir Charles Gairdner Hospital
  • S.G. Wilson
    • School of Medicine and Pharmacology University of Western Australia
    • Dept.of Endocrinology and DiabetesSir Charles Gairdner Hospital
    • Western Australian Institute of Medical Research Sir Charles Gairdner Hospital
  • F.M.A. Islam
    • School of Medicine and Pharmacology University of Western Australia
    • Western Australian Institute of Medical Research Sir Charles Gairdner Hospital
  • M. Calautti
    • Dept.of Endocrinology and DiabetesSir Charles Gairdner Hospital
  • I.M. Dick
    • School of Medicine and Pharmacology University of Western Australia
    • Dept.of Endocrinology and DiabetesSir Charles Gairdner Hospital
    • Western Australian Institute of Medical Research Sir Charles Gairdner Hospital
  • A. Devine
    • School of Medicine and Pharmacology University of Western Australia
    • Dept.of Endocrinology and DiabetesSir Charles Gairdner Hospital
    • Western Australian Institute of Medical Research Sir Charles Gairdner Hospital
    • School of Medicine and Pharmacology University of Western Australia
    • Dept.of Endocrinology and DiabetesSir Charles Gairdner Hospital
    • Western Australian Institute of Medical Research Sir Charles Gairdner Hospital
Article

DOI: 10.1007/s00223-004-0291-x

Cite this article as:
Mullin, B., Wilson, S., Islam, F. et al. Calcif Tissue Int (2005) 77: 145. doi:10.1007/s00223-004-0291-x

Abstract

Osteoporosis is known to have a strong genetic basis. It has been proposed that polymorphisms within the KL (klotho) gene have a significant effect on aging, in particular, the osteoblast defect of aging. The association between polymorphisms within this gene and biochemical markers of bone formation and resorption, bone structure, and fracture rates was studied in 1,190 postmenopausal women with a mean age of 75 years. Genotyping of these polymorphic sites was carried out using Matrix-Assisted Laser Desorption Ionization—Time of Flight (MALDI-ToF) mass spectrometry. The G allele of SNP c.1775G>A was associated with a lower osteocalcin level than the A allele (P = 0.004) in a codominant model. SNPs C-387T and IVS1+8262c>t both showed nonsignificant associations with osteocalcin (P values of 0.063 and 0.068, respectively), but a haplotype analysis of 2 of 5 haplotypes of the three SNPs with a frequency greater than 4% revealed a significant association with osteocalcin (P = 0.036). None of the individual polymorphisms or haplotypes analyzed showed any associations with a marker of bone resorption the deoxypyridinoline creatinine ratio, bone structure, or fracture data. Therefore, the G polymorphism within the c.1775G>A SNP site and a haplotype including this are associated with a reduced osteoblast product osteocalcin. These data suggest that variation in the KL gene product affects osteoblast activity independent of osteoclast activity but that this defect does not result in an effect on bone structure in this population, perhaps because of “rescue” by other genetic or environmental factors in this population.

Key words

klothoOsteoporosisBone mineral densityOsteocalcin

Copyright information

© Springer Science+Business Media, Inc. 2005