SIRT1 genetic variation is related to body mass index and risk of obesity

  1. M. Carola Zillikens, MD (m.c.zillikens{at},
  2. Joyce B.J. van Meurs, PhD1,
  3. Fernando Rivadeneira, MD, PhD1,2,
  4. Najaf Amin, MSc2,
  5. Albert Hofman, MD, PhD2,
  6. Ben A Oostra, PhD3,
  7. Eric J.G. Sijbrands, MD, PhD1,
  8. Jacqueline C.M. Witteman, PhD2,
  9. Huibert A.P. Pols, MD, PhD1,2,
  10. Cornelia M. van Duijn, PhD2 and
  11. André G. Uitterlinden, PhD1,2
  1. 1Department of Internal Medicine and
  2. 2Department of Epidemiology and
  3. 3Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands


    Objective SIRT1 has pleiotropic metabolic functions. We investigated whether SIRT1 genetic variation is associated with obesity.

    Research Design and Methods In 6251 elderly subjects from the prospective, population-based Rotterdam Study (RS), three Single Nucleotide Polymorphisms (SNPs) in the SIRT1 gene were studied in relation with body mass index (BMI) and risk of obesity (BMI ≥ 30kg/m2) and prospectively with BMI-change after 6.4 years follow-up. We used cross-sectional data from 2347 participants from the Erasmus Rucphen Family (ERF) study for replication.

    Results Minor alleles of rs7895833 (G=20.2%) and rs1467568 (A=36.8%) were associated with lower BMI in the RS (P=0.02 and 0.04) and in the replication cohort ERF (P=0.03 and 0.008) and in studies combined (P=0.002 for both SNPs) with 0.2-0.4 kg/m2 decrease in BMI per allele copy. Carriers of these alleles had 13-18% decreased risk of obesity; odds ratio (95%CI) for rs7895833 the RS: 0.79 (0.67-0.94), P=0.007; in ERF: 0.93 (0.73-1.19), P=0.37 and in the studies combined 0.87 (0.77-0.97), P=0.02; for rs1467568 in the RS: 0.80 (0.68-0.94), P=0.007; in ERF: 0.85 (0.72-0.99), P=0.04 and in the studies combined: 0.82 (0.73-0.92), P=0.0009. In the RS, the two variants were also associated with lower BMI increase during 6.4 years of follow-up (P=0.01 and 0.08).

    Conclusions Two common variants in SIRT1 are associated with lower BMI in two independent Dutch populations. Carriers of these variants have 13-18% decreased risk of obesity and gain less weight over time. The availability of SIRT1 stimulators makes these findings relevant in light of the growing obesity epidemic.


      • Received April 10, 2009.
      • Accepted August 27, 2009.