title: Polymorphisms in the macrophage migration inhibitory factor gene and bone loss in postmenopausal women.
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 -173 bp upstream of the transcriptional start site. Bone loss was estimated both by the change in BMD over 5 years 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 5 years 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 5 year 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.
authors.affiliation: Clinical and Molecular Osteoporosis Research Unit, Lund University, Department of Clinical Sciences, Malmö University Hospital, Entrance 21, Floor 4, UMAS, SE-20502 Malmö, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Swanberg
authors.forename: Fiona
authors.initials: F
authors.lastname: McGuigan
authors.forename: Kaisa K
authors.initials: KK
authors.lastname: Ivaska
authors.forename: Paul
authors.initials: P
authors.lastname: Gerdhem
authors.forename: Ulf H
authors.initials: UH
authors.lastname: Lerner
authors.forename: Richard
authors.initials: R
authors.lastname: Bucala
authors.forename: George
authors.initials: G
authors.lastname: Kuchel
authors.forename: Anne
authors.initials: A
authors.lastname: Kenny
authors.forename: Kristina
authors.initials: K
authors.lastname: Akesson
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000235:genetics; D001862:Bone Resorption / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006239:Haplotypes / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D007527:Isoenzymes / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017698:Postmenopause / Q000235:genetics*; D000071681:Tartrate-Resistant Acid Phosphatase
chemical_list: D015415:Biomarkers; D007527:Isoenzymes; D008263:Macrophage Migration-Inhibitory Factors; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
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