title: PPARG by dietary fat interaction influences bone mass in mice and humans.
abstract: Adult BMD, an important risk factor for fracture, is the result of genetic and environmental interactions. A quantitative trait locus (QTL) for the phenotype of volumetric BMD (vBMD), named Bmd8, was found on mid-distal chromosome (Chr) 6 in mice. This region is homologous to human Chr 3p25. The B6.C3H-6T (6T) congenic mouse was previously created to study this QTL. Using block haplotyping of the 6T congenic region, expression analysis in the mouse, and examination of nonsynonymous SNPs, peroxisome proliferator activated receptor gamma (Pparg) was determined to be the most likely candidate gene for the Bmd8 QTL of the 630 genes located in the congenic region. Furthermore, in the C3H/HeJ (C3H) strain, which is the donor strain for the 6T congenic, several polymorphisms were found in the Pparg gene. On challenge with a high-fat diet, we found that the 6T mouse has a lower areal BMD (aBMD) and volume fraction of trabecular bone (BV/TV%) of the distal femur compared with B6 mice. Interactions between SNPs in the PPARG gene and dietary fat for the phenotype of BMD were examined in the Framingham Offspring Cohort. This analysis showed that there was a similar interaction of the PPARG gene and diet (fat intake) on aBMD in both men and women. These findings suggest that dietary fat has a significant influence on BMD that is dependent on the alleles present for the PPARG gene.
authors: The Jackson Laboratory, Bar Harbor, Maine 04609, USA.
authors: Cheryl L
authors: CL
authors: Ackert-Bicknell
authors: Serkalem
authors: S
authors: Demissie
authors: Caralina
authors: C
authors: Marín de Evsikova
authors: Yi-Hsiang
authors: YH
authors: Hsu
authors: Victoria E
authors: VE
authors: DeMambro
authors: David
authors: D
authors: Karasik
authors: L Adrienne
authors: LA
authors: Cupples
authors: Jose M
authors: JM
authors: Ordovas
authors: Katherine L
authors: KL
authors: Tucker
authors: Kelly
authors: K
authors: Cho
authors: Ernesto
authors: E
authors: Canalis
authors: Beverly
authors: B
authors: Paigen
authors: Gary A
authors: GA
authors: Churchill
authors: Jiri
authors: J
authors: Forejt
authors: Wesley G
authors: WG
authors: Beamer
authors: Serge
authors: S
authors: Ferrari
authors: Mary L
authors: ML
authors: Bouxsein
authors: Douglas P
authors: DP
authors: Kiel
authors: Clifford J
authors: CJ
authors: Rosen
mesh_terms: D000483:Alleles; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D001842:Bone and Bones / Q000033:anatomy & histology*; D015331:Cohort Studies; D004041:Dietary Fats / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009929:Organ Size / Q000187:drug effects; D010024:Osteoporosis / Q000235:genetics; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000187:drug effects; D017422:Sequence Analysis, DNA
chemical_list: D004041:Dietary Fats; D047495:PPAR gamma