PPARG by dietary fat interaction influences bone mass in mice and humans
PPARG by dietary fat interaction influences bone mass in mice and humans
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DOI：
10.1359/jbmr.080419
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发表时间：
2008-09-01
影响因子：
6.2
通讯作者：
Rosen, Clifford J.
中科院分区：
文献类型：
--
作者：
Ackert-Bicknell, Cheryl L.;Demissie, Serkalem;Rosen, Clifford J.
成人骨密度是遗传和环境相互作用的结果，是骨折的重要危险因素。在小鼠第6染色体上发现了一个与体积骨密度（vBMD）表型相关的数量性状位点（QTL），命名为Bmd 8。该区域与人Chr 3 p25同源。先前创建了B6.C3H-6 T（6 T）同源小鼠以研究该QTL。使用块单体型分析的6 T同源区，在小鼠中的表达分析，和检查非同义SNP，过氧化物酶体增殖物激活受体γ（Pparg）被确定为最有可能的候选基因Bmd 8 QTL的630个基因位于同源区。此外，在C3 H/HeJ（C3 H）株，这是6 T同源基因的供体株，几个多态性被发现在Pparg基因。挑战高脂肪饮食。结果发现，6 T小鼠股骨远端的骨密度（aBMD）和骨小梁体积分数（BV/TV%）低于136小鼠。在Fragrance后代队列中检查PPARG基因和膳食脂肪中SNP之间的相互作用对BMD表型的影响。这项分析表明，PPARG基因和饮食（脂肪摄入）对男性和女性的aBMD有类似的相互作用。这些发现表明，膳食脂肪对BMD有显着影响，这取决于PPARG基因的等位基因。
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.