title: SIRT1 genetic variation is related to BMI and risk of obesity.
abstract: OBJECTIVE
  SIRT1 has pleiotropic metabolic functions. We investigated whether SIRT1 genetic variation is associated with obesity.
  
  
  METHODS
  In 6,251 elderly subjects from the prospective, population-based Rotterdam Study, three single nucleotide polymorphisms (SNPs) in the SIRT1 gene were studied in relation to BMI and risk of obesity (BMI > or =30 kg/m(2)) and prospectively with BMI change after 6.4 years of follow-up. We used cross-sectional data from 2,347 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 Rotterdam Study (P = 0.02 and 0.04) and in the replication cohort ERF study (P = 0.03 and 0.008) and in both studies combined (P = 0.002 for both SNPs), with a 0.2-0.4 kg/m(2) decrease in BMI per allele copy. Carriers of these alleles had 13-18% decreased risk of obesity (for rs7895833 in the Rotterdam Study: odds ratio 0.79 [95% CI 0.67-0.94], P = 0.007; in the ERF study: 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 Rotterdam Study: 0.80 [0.68-0.94], P = 0.007; in the ERF study: 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 Rotterdam Study, the two variants were also associated with a 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.
authors.affiliation: Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. m.c.zillikens@erasmusmc.nl
authors.forename: M Carola
authors.initials: MC
authors.lastname: Zillikens
authors.forename: Joyce B J
authors.initials: JB
authors.lastname: van Meurs
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Najaf
authors.initials: N
authors.lastname: Amin
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Eric J G
authors.initials: EJ
authors.lastname: Sijbrands
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: Huibert A P
authors.initials: HA
authors.lastname: Pols
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
mesh_terms: D000368:Aged; D015992:Body Mass Index; D005260:Female; D005500:Follow-Up Studies; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D009426:Netherlands / Q000453:epidemiology; D009765:Obesity / Q000453:epidemiology / Q000235:genetics*; D050177:Overweight / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D018570:Risk Assessment; D056564:Sirtuin 1 / Q000235:genetics*
chemical_list: C447939:SIRT1 protein, human; D056564:Sirtuin 1