PPARG by dietary fat interaction influences bone mass in mice and humans

被引：13

作者：

Ackert-Bicknell, Cheryl L. ^{[1
]}

Demissie, Serkalem ^{[2
]}

de Evsikova, Caralina Marin ^{[1
]}

Hsu, Yi-Hsiang ^{[3
,4
,5
]}

DeMambro, Victoria E. ^{[1
]}

Karasik, David ^{[4
,5
]}

Cupples, L. Adrienne ^{[2
]}

Ordovas, Jose M. ^{[6
]}

Tucker, Katherine L. ^{[6
]}

Cho, Kelly ^{[2
]}

Canalis, Ernesto ^{[7
,8
]}

Paigen, Beverly ^{[1
]}

Churchill, Gary A. ^{[1
]}

Forejt, Jiri ^{[9
]}

Beamer, Wesley G. ^{[1
]}

Ferrari, Serge ^{[10
]}

Bouxsein, Mary L. ^{[5
,11
]}

Kiel, Douglas P. ^{[4
,5
]}

Rosen, Clifford J. ^{[1
]}

机构：

[1] Jackson Lab, Bar Harbor, ME 04609 USA

[2] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA

[3] Harvard Univ, Sch Publ Hlth, Program Populat Genet, Boston, MA 02115 USA

[4] Inst Aging Res, Boston, MA USA

[5] Harvard Univ, Sch Med, Boston, MA USA

[6] Tufts Univ, Jean Mayer USDA, Human Nutr Res Ctr Aging, Boston, MA 02111 USA

[7] St Francis Hosp & Med Ctr, Dept Res, Hartford, CT 06105 USA

[8] Univ Connecticut, Sch Med, Farmington, CT USA

[9] Acad Sci Czech Republ, Inst Mol Genet, Prague, Czech Republic

[10] Univ Hosp Geneva, WHO, Ctr Osteoporosis Prevent, Dept Rehabil & Geriatr,Serv Bone Dis, Geneva, Switzerland

[11] Beth Israel Deaconess Med Ctr, Orthoped Biomech Lab, Boston, MA 02215 USA

来源：

JOURNAL OF BONE AND MINERAL RESEARCH | 2008年 / 23卷 / 09期

关键词：

skeletal genetics; animal models; candidate gene; environmental interaction; human population;

D O I：

10.1359/JBMR.080419

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

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 ha a lower areal BMD (aBMD) and volume fraction of trabecular bone (BV/TV%) of the distal femur compared with 136 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 oil the alleles present for the PPARG gene.

引用

页码：1398 / 1408

页数：11

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