TY - JOUR
T1 - PPARG by dietary fat interaction influences bone mass in mice and humans
AU - Ackert-Bicknell, Cheryl L.
AU - Demissie, Serkalem
AU - Marín de Evsikova, Caralina
AU - Hsu, Yi Hsiang
AU - DeMambro, Victoria E.
AU - Karasik, David
AU - Cupples, L. Adrienne
AU - Ordovas, Jose M.
AU - Tucker, Katherine L.
AU - Cho, Kelly
AU - Canalis, Ernesto
AU - Paigen, Beverly
AU - Churchill, Gary A.
AU - Forejt, Jiri
AU - Beamer, Wesley G.
AU - Ferrari, Serge
AU - Bouxsein, Mary L.
AU - Kiel, Douglas P.
AU - Rosen, Clifford J.
PY - 2008/9
Y1 - 2008/9
N2 - 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 γ (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.
AB - 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 γ (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.
KW - Animal models
KW - Candidate gene
KW - Environmental interaction
KW - Human population
KW - Skeletal genetics
UR - http://www.scopus.com/inward/record.url?scp=50249169333&partnerID=8YFLogxK
U2 - 10.1359/jbmr.080419
DO - 10.1359/jbmr.080419
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C2 - 18707223
AN - SCOPUS:50249169333
SN - 0884-0431
VL - 23
SP - 1398
EP - 1408
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 9
ER -
