title: Association of sirtuin 1 (SIRT1) gene SNPs and transcript expression levels with severe obesity.
abstract: Recent studies have reported associations of sirtuin 1 (SIRT1) single nucleotide polymorphisms (SNPs) to both obesity and BMI. This study was designed to investigate association between SIRT1 SNPs, SIRT1 gene expression and obesity. Case-control analyses were performed using 1,533 obese subjects (896 adults, BMI >40 kg/m(2) and 637 children, BMI >97th percentile for age and sex) and 1,237 nonobese controls, all French Caucasians. Two SNPs (in high linkage disequilibrium (LD), r(2) = 0.96) were significantly associated with adult obesity, rs33957861 (P value = 0.003, odds ratio (OR) = 0.75, confidence interval (CI) = 0.61-0.92) and rs11599176 (P value: 0.006, OR = 0.74, CI = 0.61-0.90). Expression of SIRT1 mRNA was measured in BMI-discordant siblings from 154 Swedish families. Transcript expression was significantly correlated to BMI in the lean siblings (r(2) = 0.13, P value = 3.36 × 10(-7)) and lower SIRT1 expression was associated with obesity (P value = 1.56 × 10(-35)). There was also an association between four SNPs (rs11599176, rs12413112, rs33957861, and rs35689145) and BMI (P values: 4 × 10(-4), 6 × 10(-4), 4 × 10(-4), and 2 × 10(-3)) with the rare allele associated with a lower BMI. However, no SNP was associated with SIRT1 transcript expression level. In summary, both SNPs and SIRT1 gene expression are associated with severe obesity.
authors.affiliation: Department of Genomics of Common Diseases, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Clark
authors.forename: Mario
authors.initials: M
authors.lastname: Falchi
authors.forename: Bob
authors.initials: B
authors.lastname: Olsson
authors.forename: Peter
authors.initials: P
authors.lastname: Jacobson
authors.forename: Stéphane
authors.initials: S
authors.lastname: Cauchi
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantieri
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Andersson
authors.forename: Margareta
authors.initials: M
authors.lastname: Jernås
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Aitman
authors.forename: Sylvia
authors.initials: S
authors.lastname: Richardson
authors.forename: Lars
authors.initials: L
authors.lastname: Sjöström
authors.forename: Hang Y
authors.initials: HY
authors.lastname: Wong
authors.forename: Lena M S
authors.initials: LM
authors.lastname: Carlsson
authors.forename: Philippe
authors.initials: P
authors.lastname: Froguel
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Walley
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D016022:Case-Control Studies; D002648:Child; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009767:Obesity, Morbid / Q000453:epidemiology / Q000235:genetics*; D016017:Odds Ratio; D047495:PPAR gamma / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D035781:Siblings; D056564:Sirtuin 1 / Q000235:genetics*; D013548:Sweden / Q000453:epidemiology; D015854:Up-Regulation; D044465:White People / Q000235:genetics
chemical_list: D047495:PPAR gamma; D056564:Sirtuin 1