Association Study of Sirtuin 1 Polymorphisms With Bone Mineral Density and Body Mass Index

Arch Med Res. 2012 Jul;43(5):363-8. doi: 10.1016/j.arcmed.2012.06.012. Epub 2012 Jul 21.


Background and aims: Sirtuin 1, encoded by the SIRT1 gene, is an emerging modulator of carbohydrate and lipid metabolism and may also influence the differentiation of bone cells. Our objective was to test the hypothesis that polymorphisms of SIRT1 are associated with body mass index (BMI) and bone mineral density (BMD).

Methods: We carried out a cross-sectional genetic association study with genotyping of ten single nucleotide polymorphisms of the SIRT1 region. The discovery cohort included 1394 individuals (342 males, 1052 females). Significant results were replicated in an independent cohort of 408 males.

Results: We did not find a significant association of genotypes with BMD. There were also no significant BMI differences across genotypes in females. However, in males, two polymorphisms tended to be associated with BMI in the discovery cohort (p 0.03 and 0.05). A similar trend was also observed in the replication cohort. Thus, in the combined analysis of both cohorts, males with C alleles at the rs12049646 locus had a lower BMI than TT homozygotes, with a mean difference of 0.82 kg/m(2) (95% confidence interval 0.15-1.48; p = 0.016). Differences in the DNA binding of nuclear proteins between C and T alleles were also observed in vitro.

Conclusions: These results suggest that common variants of the SIRT1 gene influence BMI but not BMD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Body Mass Index*
  • Bone Density / genetics*
  • Cross-Sectional Studies
  • Electrophoretic Mobility Shift Assay
  • Female
  • Gene Frequency
  • Genetic Association Studies
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Nuclear Proteins / chemistry
  • Polymorphism, Single Nucleotide*
  • Protein Binding
  • Sequence Analysis, DNA
  • Sirtuin 1 / genetics*


  • Nuclear Proteins
  • SIRT1 protein, human
  • Sirtuin 1