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Título

Sirtuin 1 polymorphisms, bone mass and adiposity

Autor Rodríguez-Rey, José C.; Sainz, Jesús ; Riancho, José A.
Fecha de publicación 7-may-2011
Citación 3rd Joint Meeting ECTS and IBMS (2011)
ResumenGenetic factors have an important influence on adiposity and bone mass. Sirtuin 1, encoded by the SIRT1 gene, is an emerging important modulator of carbohydrate and lipid metabolism and may also influence the differentiation of bone cells. Our aim was to explore whether common polymorphisms of SIRT1 influence body mass index (BMI) and bone mineral density (BMD). Ten single nucleotide polymorphisms capturing most common variations of the SIRT1 genomic region were genotyped in 1394 Spanish individuals by using Taqman assays. The association of genotypes with BMI and BMD was explored. Significant results were replicated in an independent cohort of 408 men. SIRT1 gene expression was also determined in bone samples from patients with osteoporotic fractures and controls by real time qPCR. Allelic differences in the binding of transcription factors were studied in vitro. There were no significant associations between the genotypes and BMD. SIRT1 expression level was similar in femoral samples of patients with osteoporotic hip fractures and controls. There were no significant BMI differences across genotypes in women. However, in men, two polymorphisms were associated with BMI (p = 0.03 and 0.05). A similar trend was also observed in an independent male cohort. Thus, in the combined analysis men with C alleles at the rs12049646 locus had a lower BMI than TT homozygotes, with a mean difference of 0.8 kg/m2 (p = 0.016). Electrophoretic shift mobility assays revealed differences in the binding of nuclear proteins to C and T alleles. These results suggest that common variants of the SIRT1 gene may influence BMI. However, we found no evidence for association with BMD.
Descripción Trabajo presentado al: "3rd Joint Meeting European Calcified Tissue Society and International Bone and Mineral Society" celebrado en Atenas (Grecia) del 7 al 11 de mayo de 2011.-- et al.
URI http://hdl.handle.net/10261/89006
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