Interactions between Dietary Fat Intake and FASN Genetic Variation Influence LDL Peak Particle Diameter

<i>Background:</i> The small, dense LDL phenotype is associated with an increased cardiovascular disease risk. A genome-wide scan performed on the Quebec Family Study (QFS) revealed a quantitative trait locus for LDL peak particle diameter (LDL-PPD) on the 17q21 region. A positional candidate gene – the fatty acid synthase gene <i>(FASN)</i> – encodes a key enzyme in the biogenesis of membrane lipids. FASN may play a role in the regulation of feeding and may be a potential therapeutic target for obesity and insulin resistance. <i>Methods:</i> Analyses were performed on 592 subjects of the QFS. Dietary fat was estimated by a 3-day food record. LDL-PPD was measured by gradient gel electrophoresis on polyacrylamide gradient gels. <i>Results:</i> Five single nucleotide polymorphisms were genotyped in <i>FASN</i> gene. <i>FASN</i> rs4246444 was associated with LDL-PPD, but only when fat intake was taken into account (p = 0.001). High and low lipid consumers were defined using a cutoff of 35% of dietary fat intake. Carriers of the variant allele showed smaller LDL-PPD only when consuming a high amount of fat. This association remained significant after adjustments for age, sex, body mass index and plasma triglyceride levels. <i>Conclusion:</i> The results suggest that dietary fat intake may modify the effect of the <i>FASN</i> rs4246444 polymorphism on LDL-PPD.