Advanced

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

Swanberg, Maria LU ; McGuigan, Fiona LU ; Ivaska, Kaisa LU ; Gerdhem, Paul LU ; Lerner, Ulf H; Bucala, Richard; Kuchel, George; Kenny, Anne and Åkesson, Kristina LU (2010) In Bone 47. p.424-429
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Bone
volume
47
pages
424 - 429
publisher
Elsevier
external identifiers
  • WOS:000280449300031
  • PMID:20471506
  • Scopus:77955985353
ISSN
1873-2763
DOI
10.1016/j.bone.2010.05.009
language
English
LU publication?
yes
id
6de8ffa6-7945-4ca4-9c9d-f872ffbe4ccb (old id 1610225)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20471506?dopt=Abstract
date added to LUP
2010-06-02 10:45:00
date last changed
2016-10-13 04:34:21
@misc{6de8ffa6-7945-4ca4-9c9d-f872ffbe4ccb,
  abstract     = {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&lt;0.05) and total hip (p&lt;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&lt;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.},
  author       = {Swanberg, Maria and McGuigan, Fiona and Ivaska, Kaisa and Gerdhem, Paul and Lerner, Ulf H and Bucala, Richard and Kuchel, George and Kenny, Anne and Åkesson, Kristina},
  issn         = {1873-2763},
  language     = {eng},
  pages        = {424--429},
  publisher    = {ARRAY(0xb87cab0)},
  series       = {Bone},
  title        = {Polymorphisms in the macrophage migration inhibitory factor gene and bone loss in postmenopausal women.},
  url          = {http://dx.doi.org/10.1016/j.bone.2010.05.009},
  volume       = {47},
  year         = {2010},
}