title: Polymorphisms of the peroxisome proliferator-activated receptor γ (PPARγ) gene are associated with osteoporosis.
abstract: Stimulation of PPARγ turns mesenchymal stem cells into adipocytes instead of osteoblasts. We investigated the effect of polymorphisms in the PPARγ gene on BMD and fracture risk in two Danish cohorts and found opposing effects of certain SNPs and haplotypes in the two cohorts probably owing to environmental factors.
  
  
  BACKGROUND
  Stimulation of PPARγ causes development of mesenchymal stem cells to adipocytes instead of osteoblasts leading to decreased osteoblast number and BMD. The aim of this study was to examine the effect of PPARG polymorphisms on BMD and fracture risk in two Danish cohorts: AROS, a case-control population comprising 809 individuals and DOPS, a population comprising 1,716 perimenopausal women allocated to hormone therapy or not at baseline and followed for 10 years. On the basis of linkage disequilibrium between SNPs throughout the gene and previous studies we chose 10 polymorphisms for investigation.
  
  
  METHODS
  In AROS, individuals heterozygous for the polymorphisms rs12497191, rs4135263, and rs1151999 had an increased risk of vertebral fractures (OR = 1.48-1.76, p = 0.005-0.04) compared with individuals homozygous for the common allele. In DOPS, individuals heterozygous for rs1151999 had an increased BMD at the hip sites (p ≤ 0.02). An interaction between rs1151999 and diet was found on BMD in both cohorts.
  
  
  RESULTS
  For the polymorphism rs1152003 there was an interaction with body weight on BMD at all sites in both cohorts (p ≤ 0.07). Stratified analyses revealed that in the high weight group in AROS individuals homozygous for the variant allele had a decreased BMD (p ≤ 0.02), whereas the same pattern was found in the low weight group in DOPS (p ≤ 0.03). A number of haplotype associations were found as well, the direction of which was opposite in the two cohorts.
  
  
  CONCLUSIONS
  Our study suggests an association SNPs in PPARG and haplotypes thereof and BMD and fracture risk. The effect however appears to be modifiable by environmental factors.
authors.affiliation: Department of Endocrinology and Internal Medicine THG, Aarhus University Hospital, 8000, Århus C, Denmark. torbhars@rm.dk
authors.forename: T
authors.initials: T
authors.lastname: Harsløf
authors.forename: C L
authors.initials: CL
authors.lastname: Tofteng
authors.forename: L B
authors.initials: LB
authors.lastname: Husted
authors.forename: M
authors.initials: M
authors.lastname: Nyegaard
authors.forename: A
authors.initials: A
authors.lastname: Børglum
authors.forename: M
authors.initials: M
authors.lastname: Carstens
authors.forename: L
authors.initials: L
authors.lastname: Stenkjær
authors.forename: K
authors.initials: K
authors.lastname: Brixen
authors.forename: P
authors.initials: P
authors.lastname: Eiken
authors.forename: J-E B
authors.initials: JE
authors.lastname: Jensen
authors.forename: L
authors.initials: L
authors.lastname: Mosekilde
authors.forename: L
authors.initials: L
authors.lastname: Rejnmark
authors.forename: B L
authors.initials: BL
authors.lastname: Langdahl
mesh_terms: D000328:Adult; D000368:Aged; D001835:Body Weight; D015519:Bone Density / Q000235:genetics*; D016022:Case-Control Studies; D004032:Diet; D005260:Female; D006239:Haplotypes; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000150:complications / Q000235:genetics*; D058866:Osteoporotic Fractures / Q000209:etiology; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D016103:Spinal Fractures / Q000209:etiology
chemical_list: D047495:PPAR gamma