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Published on: June 4, 2014
Interactions between dietary fat intake and FASN genetic variation influence LDL peak particle diameter
G Dolley1, M E Boisclair, B Lamarche
1Institute of Nutraceuticals and Functional Foods (INAF), Laval University, Quebec, Canada.
Background:
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 (FASN) - 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.
Methods:
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.
Results:
Five single nucleotide polymorphisms were genotyped in FASN gene. FASN 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.
Conclusion:
The results suggest that dietary fat intake may modify the effect of the FASN rs4246444 polymorphism on LDL-PPD.
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