Abstract 5056: Postprandial Lipemia Is Modified by the Presence of Common Genetic Variations at the FTO Gene in a Caucasian Population
Background: Several FTO (fat mass and obesity associated) polymorphic sites have been studied for their potential use as markers for obesity and the metabolic syndrome. Its mechanism of action has not been elucidated, although recent studies point to a role of FTO in the regulation of adipocyte lipolysis.
Hypothesis: In view of these evidences and the relation between adipocyte lipolysis and postprandial lipid metabolism, we hypothesized that FTO variants may affect postprandial lipid metabolism. Therefore, we investigated whether the presence of common genetic variations at the FTO rs1121980C>T, rs9339609T>A and rs9330506A>G influence postprandial lipoprotein metabolism in a healthy Caucasian population.
Methods: 88 volunteers were given a fat-rich meal containing 1 g fat and 7 mg cholesterol per kg body weight and vitaminA60,000 IU/m2 body surface. Fat accounted for 60% of calories, and protein and carbohydrates for 15 and 25% of energy, respectively. Blood samples were taken at time 0, every 1 h until 6 h, and every 2.5 h until 11 h. Total cholesterol and triacylglycerols (TAGs), and TAGs in triacylglycerol-rich lipoproteins (TRL) (large and small TRL) were determined by ultracentrifugation.
Results: Linkage disequilibrium (LD) was highly significant among all the SNPs examined. Therefore, we display the results only for rs1121980C>T as a tag SNP (genotype frequencies: 27 C/C, 44 C/T and 17 T/T). Individuals carrying the T/T genotype presented lower postprandial concentrations of plasma TAGs (P = 0.019) and TAGs in small-TRL (P=0.015) than did carriers of the major C allele. Consistently, the area under curve for TAGs (P=0.016) and small-TRL TAGs (P=0.021) was lower in T/T individuals compared with the other two groups. No other statistically significant genotype related differences for other parameters were observed.
Conclusions: Our findings suggest that the presence of the minor allele T at the FTO is associated with a lower postprandial response which may result in lower atherogenic risk for these individuals.