A missense single nucleotide polymorphism, V114I of the Werner syndrome gene, is associated with risk of osteoporosis and femoral fracture in the Japanese population

Heying Zhou, Seijiro Mori*, Masashi Tanaka, Motoji Sawabe, Tomio Arai, Masaaki Muramatsu, Makiko Naka Mieno, Shoji Shinkai, Yoshiji Yamada, Motohiko Miyachi, Haruka Murakami, Kiyoshi Sanada, Hideki Ito

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Werner syndrome is a rare autosomal recessive disorder caused by mutations in the human WRN gene and characterized by the early onset of normal aging symptoms. Given that patients with this disease exhibit osteoporosis, the present study aimed to determine whether the WRN gene contributes to the etiology of osteoporosis. A genetic association study of eight non-synonymous polymorphisms in the WRN gene and the incidence of femoral fracture was undertaken in 1,632 consecutive Japanese autopsies in which 140 patients had experienced the fracture during their lifetime. The results were validated in 251 unrelated postmenopausal Japanese women with osteoporosis and 269 non-institutionalized, community-dwelling Japanese adults. A statistically significant association was observed between rs2230009 (c.340G > A)—which results in a Val to Ile substitution—and fracture risk; the incidence of femoral fracture increased dose-dependently with the number of A alleles (p = 0.0120). Femoral neck bone and whole bone densities were lower among postmenopausal women with osteoporosis and community-dwelling adults, respectively, if they were of the AG instead of the GG genotype. The results suggest that Japanese subjects bearing at least one A allele of rs2230009 of the WRN gene are at a significantly higher risk of femoral fracture, possibly due to decreased bone density.

Original languageEnglish
Pages (from-to)694-700
Number of pages7
JournalJournal of Bone and Mineral Metabolism
Volume33
Issue number6
DOIs
Publication statusPublished - 2015 Nov 1
Externally publishedYes

Keywords

  • Femoral fracture
  • Osteoporosis
  • Single nucleotide polymorphism
  • Werner syndrome

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Endocrinology

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