Association of Sirtuin 1 ( ) Gene SNPs and Transcript Expression Levels With Severe Obesity

• Published in: Obesity (Silver Spring, Md.) Md.), 2012-01, Vol.20 (1), p.178-185
• Main Authors: Clark, Stephen J., Falchi, Mario, Olsson, Bob, Jacobson, Peter, Cauchi, Stéphane, Balkau, Beverley, Marre, Michel, Lantieri, Olivier, Andersson, Johanna C., Jernås, Margareta, Aitman, Timothy J., Richardson, Sylvia, Sjöström, Lars, Wong, Hang Y., Carlsson, Lena M. S., Froguel, Philippe, Walley, Andrew J.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Biochemistry and Molecular Biology; Biokemi och molekylärbiologi; BMI; Body Mass Index; Case-Control Studies; Child; Female; gene expression; Gene Expression Regulation, Enzymologic; Genetic Predisposition to Disease; Genetics; Genetik; Humans; Male; Obesity; Obesity, Morbid - epidemiology; Obesity, Morbid - genetics; Odds Ratio; Polymorphism, Single Nucleotide; PPAR gamma - genetics; Siblings; sirtuin 1; Sirtuin 1 - genetics; SNP; Sweden - epidemiology; Up-Regulation; White People - genetics
• ISSN: 1930-7381; 1930-739X
• DOI: 10.1038/oby.2011.200

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/m2 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), r2 = 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 (r2 = 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.