Association of Sirtuin 1 (SIRT1) Gene SNPs and Transcript Expression Levels With Severe Obesity

作者：Clark Stephen J; Falchi Mario; Olsson Bob; Jacobson Peter; Cauchi Stephane; Balkau Beverley; Marre Michel; Lantieri Olivier; Andersson Johanna C; Jernas Margareta; Aitman Timothy J; Richardson Sylvia; Sjostrom Lars; Wong Hang Y; Carlsson Lena M S; Froguel Philippe; Walley Andrew J^*

来源：Obesity, 2012, 20(1): 178-185.

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 %26gt;40 kg/m(2) and 637 children, BMI %26gt;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 x 10(-7)) and lower SIRT1 expression was associated with obesity (P value = 1.56 x 10(-35)). There was also an association between four SNPs (rs11599176, rs12413112, rs33957861, and rs35689145) and BMI (P values: 4 x 10(-4), 6 x 10(-4), 4 x 10(-4), and 2 x 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.

• 出版日期2012-1