title: The postprandial chylomicron triacylglycerol response to dietary fat in healthy male adults is significantly explained by a combination of single nucleotide polymorphisms in genes involved in triacylglycerol metabolism.
abstract: BACKGROUND
  The postprandial chylomicron (CM) triacylglycerol (TG) response to dietary fat, which is positively associated with atherosclerosis and cardiovascular disease risk, displays a high interindividual variability. This is assumed to be due, at least partly, to polymorphisms in genes involved in lipid metabolism. Existing studies have focused on single nucleotide polymorphisms (SNPs), resulting in only a low explained variability.
  
  
  OBJECTIVE
  We aimed to identify a combination of SNPs associated with the postprandial CM TG response.
  
  
  METHODS
  Thirty-three healthy male volunteers were subjected to 4 standardized fat tolerance test meals (to correct for intraindividual variability) and genotyped using whole-genome microarrays. The plasma CM TG concentration was measured at regular interval times after each meal. The association of SNPs in or near candidate genes (126 genes representing 6225 SNPs) with the postprandial CM TG concentration (0-8 h areas under the curve averaged for the 4 test meals) was assessed by partial least squares regression, a multivariate statistical approach.
  
  
  RESULTS
  Data obtained allowed us to generate a validated significant model (P = 1.3 × 10(-7)) that included 42 SNPs in 23 genes (ABCA1, APOA1, APOA5, APOB, BET1, CD36, COBLL1, ELOVL5, FRMD5, GPAM, INSIG2, IRS1, LDLR, LIPC, LPL, LYPLAL1, MC4R, NAT2, PARK2, SLC27A5, SLC27A6, TCF7L2, and ZNF664) and explained 88% of the variance. In 39 of these SNPs, univariate analysis showed that subjects with different genotypes exhibited significantly different (q < .05) postprandial CM TG responses.
  
  
  CONCLUSIONS
  Using a multivariate approach, we report a combination of SNPs that explains a significant part of the variability in the postprandial CM TG response.
authors.affiliation: Institut National de la Recherche Agronomique (INRA), Unité Mixte de Recherche (UMR) INRA1260, F-13005, Marseille, France; Inserm, UMR_S 1062, F-13005, Marseille, France; and Aix-Marseille Université, Nutrition, Obésité et Risques Thrombotiques, F-13005, Marseille, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Desmarchelier
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Martin
authors.forename: Richard
authors.initials: R
authors.lastname: Planells
authors.forename: Marguerite
authors.initials: M
authors.lastname: Gastaldi
authors.forename: Marion
authors.initials: M
authors.lastname: Nowicki
authors.forename: Aurélie
authors.initials: A
authors.lastname: Goncalves
authors.forename: René
authors.initials: R
authors.lastname: Valéro
authors.forename: Denis
authors.initials: D
authors.lastname: Lairon
authors.forename: Patrick
authors.initials: P
authors.lastname: Borel
mesh_terms: D000328:Adult; D002318:Cardiovascular Diseases / Q000235:genetics / Q000378:metabolism; D002914:Chylomicrons / Q000097:blood*; D004041:Dietary Fats / Q000008:administration & dosage*; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019518:Postprandial Period; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood* / Q000378:metabolism*
chemical_list: D002914:Chylomicrons; D004041:Dietary Fats; D014280:Triglycerides