Klotho gene polymorphisms associated with bone density of aged postmenopausal women

Ken ichi Kawano, Naoshi Ogata, Mathias Chiano, Helen Molloy, Patrick Kleyn, Tim D. Spector, Motoyuki Uchida, Takayuki Hosoi, Takao Suzuki, Hajime Orimo, Satoshi Inoue, Yoichi Nabeshima, Kozo Nakamura, Makoto Kuro-O, Hiroshi Kawaguchi

Research output: Contribution to journalArticle

139 Citations (Scopus)

Abstract

Because mice deficient in klotho gene expression exhibit multiple aging phenotypes including osteopenia, we explored the possibility that the klotho gene may contribute to age-related bone loss in humans by examining the association between klotho gene polymorphisms and bone density in two genetically distinct racial populations: the white and the Japanese. Screening of single-nucleotide polymorphisms (SNPs) in the human klotho gene identified 11 polymorphisms, and three of them were common in both populations. Associations of the common SNPs with bone density were investigated in populations of 1187 white women and of 215 Japanese postmenopausal women. In the white population, one in the promoter region (G-395A, p = 0.001) and one in exon 4 (C1818T, p = 0.010) and their haplotypes (p < 0.0001) were significantly associated with bone density in aged postmenopausal women (≥65 years), but not in premenopausal or younger postmenopausal women. These associations were also seen in Japanese postmenopausal women. An electrophoretic mobility shift analysis revealed that the G-A substitution in the promoter region affected DNA-protein interaction in cultured human kidney 293 cells. These results indicate that the klotho gene may be involved in the pathophysiology of bone loss with aging in humans.

Original languageEnglish (US)
Pages (from-to)1744-1751
Number of pages8
JournalJournal of Bone and Mineral Research
Volume17
Issue number10
StatePublished - Oct 1 2002

Fingerprint

Bone Density
Genes
Genetic Promoter Regions
Population
Single Nucleotide Polymorphism
Metabolic Bone Diseases
Haplotypes
Osteoporosis
Exons
Phenotype
Kidney
Gene Expression
Bone and Bones
DNA
Proteins

Keywords

  • Aging
  • Association
  • Genetics
  • Osteoporosis
  • Pathophysiology

ASJC Scopus subject areas

  • Surgery

Cite this

Kawano, K. I., Ogata, N., Chiano, M., Molloy, H., Kleyn, P., Spector, T. D., ... Kawaguchi, H. (2002). Klotho gene polymorphisms associated with bone density of aged postmenopausal women. Journal of Bone and Mineral Research, 17(10), 1744-1751.

Klotho gene polymorphisms associated with bone density of aged postmenopausal women. / Kawano, Ken ichi; Ogata, Naoshi; Chiano, Mathias; Molloy, Helen; Kleyn, Patrick; Spector, Tim D.; Uchida, Motoyuki; Hosoi, Takayuki; Suzuki, Takao; Orimo, Hajime; Inoue, Satoshi; Nabeshima, Yoichi; Nakamura, Kozo; Kuro-O, Makoto; Kawaguchi, Hiroshi.

In: Journal of Bone and Mineral Research, Vol. 17, No. 10, 01.10.2002, p. 1744-1751.

Research output: Contribution to journalArticle

Kawano, KI, Ogata, N, Chiano, M, Molloy, H, Kleyn, P, Spector, TD, Uchida, M, Hosoi, T, Suzuki, T, Orimo, H, Inoue, S, Nabeshima, Y, Nakamura, K, Kuro-O, M & Kawaguchi, H 2002, 'Klotho gene polymorphisms associated with bone density of aged postmenopausal women', Journal of Bone and Mineral Research, vol. 17, no. 10, pp. 1744-1751.
Kawano KI, Ogata N, Chiano M, Molloy H, Kleyn P, Spector TD et al. Klotho gene polymorphisms associated with bone density of aged postmenopausal women. Journal of Bone and Mineral Research. 2002 Oct 1;17(10):1744-1751.
Kawano, Ken ichi ; Ogata, Naoshi ; Chiano, Mathias ; Molloy, Helen ; Kleyn, Patrick ; Spector, Tim D. ; Uchida, Motoyuki ; Hosoi, Takayuki ; Suzuki, Takao ; Orimo, Hajime ; Inoue, Satoshi ; Nabeshima, Yoichi ; Nakamura, Kozo ; Kuro-O, Makoto ; Kawaguchi, Hiroshi. / Klotho gene polymorphisms associated with bone density of aged postmenopausal women. In: Journal of Bone and Mineral Research. 2002 ; Vol. 17, No. 10. pp. 1744-1751.
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