title: Interactions between dietary fat intake and FASN genetic variation influence LDL peak particle diameter.
abstract: 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.
  
  
  CONCLUSIONS
  The results suggest that dietary fat intake may modify the effect of the FASN rs4246444 polymorphism on LDL-PPD.
authors.affiliation: Institute of Nutraceuticals and Functional Foods (INAF), Laval University, Quebec, Canada.
authors.forename: G
authors.initials: G
authors.lastname: Dolley
authors.forename: M E
authors.initials: ME
authors.lastname: Boisclair
authors.forename: B
authors.initials: B
authors.lastname: Lamarche
authors.forename: J P
authors.initials: JP
authors.lastname: Després
authors.forename: C
authors.initials: C
authors.lastname: Bouchard
authors.forename: L
authors.initials: L
authors.lastname: Pérusse
authors.forename: M C
authors.initials: MC
authors.lastname: Vohl
mesh_terms: D000328:Adult; D015331:Cohort Studies; D004041:Dietary Fats / Q000008:administration & dosage*; D004591:Electrophoresis, Polyacrylamide Gel; D054890:Fatty Acid Synthase, Type I / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010316:Particle Size; D020641:Polymorphism, Single Nucleotide
chemical_list: D004041:Dietary Fats; D008077:Lipoproteins, LDL; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I