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Polymorphisms in the macrophage migration inhibitory factor gene and bone loss in postmenopausal women.

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Author

Summary, in English

Osteoporosis is a severe condition in postmenopausal women and a common cause of fracture. Osteoporosis is a complex disease with a strong genetic impact, but susceptibility is determined by many genes with modest effects and environmental factors. Only a handful of genes consistently associated with osteoporosis have been identified so far. Inflammation affects bone metabolism by interfering with the interplay between bone resorption and formation, and many inflammatory mediators are involved in natural bone remodeling. The cytokine macrophage migration inhibitory factor (MIF) has been shown to affect bone density in rodents, and polymorphisms in the human MIF promoter are associated with inflammatory disorders such as rheumatoid arthritis. We investigated the association of polymorphisms in the MIF gene with bone mineral density (BMD) and bone loss in 1002 elderly women using MIF promoter polymorphisms MIF-CATT(5)(-)(8) and rs755622(G/C) located -794 and -173bp upstream of the transcriptional start site. Bone loss was estimated both by the change in BMD over 5years and by the levels of bone resorption markers in serum measured at four occasions during a 5-year period. The MIF-CATT(7)/rs755622(C) haplotype was associated with increased rate of bone loss during 5years at the femoral neck (p<0.05) and total hip (p<0.05). In addition, the MIF-CATT(7)/rs755622(C) haplotype carriers had higher levels of the bone turnover marker serum C-terminal cross-linking telopeptide of type I collagen (S-CTX-I, p<0.01) during the 5year follow-up period. There was no association between MIF-CATT(7)/rs755622(C) and baseline BMD at femoral neck, total hip or lumbar spine. We conclude that MIF promoter polymorphisms have modest effects on bone remodeling and are associated with the rate of bone loss in elderly women.

Publishing year

2010

Language

English

Pages

424-429

Publication/Series

Bone

Volume

47

Document type

Journal article

Publisher

Elsevier

Topic

  • Orthopedics

Status

Published

Research group

  • Translational Neurogenetics
  • Orthopedics - Clinical and Molecular Osteoporosis Research

ISBN/ISSN/Other

  • ISSN: 1873-2763