title: Genetic factors associated with response of LDL subfractions to change in the nature of dietary fat.
abstract: A preponderance of dense low density lipoprotein (LDL) particles is associated with an increased risk of coronary heart disease. It has been shown that dense LDL levels can be modified by diet. We investigated the contribution of polymorphisms in the genes for apolipoprotein (apo) B, apo AIV, lipoprotein lipase (LPL) and cholesterol ester transfer protein (CETP) to variation in the changes in plasma concentrations of dense LDL between a high saturated and a high polyunsaturated fatty acid diet. A total of 46 freeliving individuals (19 men and 27 women) completed a crossover trial with two dietary interventions of 4 weeks each, a high saturated fat diet (providing 21% energy from saturated fat and 3% energy from polyunsaturated fat) and a high polyunsaturated fat diet (providing 11% energy as saturated fat and 10% energy as polyunsaturated fat). Overall, the change in dense LDL between the saturated and polyunsaturated fat period was 0.17+/-0.33 mmol/L and this change was similar in men and women. Of the polymorphisms studied only variation in the apo AIV gene causing the substitution of histidine for glutamine at position 360 (Q360H) was associated with significant differences in the change in dense LDL concentration. Apo AIV Q/H individuals (n=6) showed a three-fold greater change in dense LDL cholesterol unadjusted for Lp(a) levels than Q/Q individuals (0.46+/-0.27 versus 0.12+/-0.31 mmol/L, p=0.02). The greater decrease in dense LDL cholesterol with an increase in polyunsaturated fat seen in those with the apo AIV H360 variant, who represent roughly 10% of the general population, suggests that they may benefit most from a PUFA rich lipid lowering diet.
authors.affiliation: Department of Human Nutrition, Dunedin School of Medicine, University of Otago Medical School, Great King St, PO Box 913, Dunedin, New Zealand.
authors.forename: A J
authors.initials: AJ
authors.lastname: Wallace
authors.forename: S E
authors.initials: SE
authors.lastname: Humphries
authors.forename: R M
authors.initials: RM
authors.lastname: Fisher
authors.forename: J I
authors.initials: JI
authors.lastname: Mann
authors.forename: A
authors.initials: A
authors.lastname: Chisholm
authors.forename: W H
authors.initials: WH
authors.lastname: Sutherland
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001054:Apolipoproteins A / Q000032:analysis; D002352:Carrier Proteins / Q000032:analysis; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000032:analysis* / Q000235:genetics; D008078:Cholesterol, LDL / Q000032:analysis* / Q000235:genetics; D018592:Cross-Over Studies; D004042:Dietary Fats, Unsaturated / Q000008:administration & dosage*; D005227:Fatty Acids / Q000008:administration & dosage*; D005260:Female; D006023:Glycoproteins; D006801:Humans; D006937:Hypercholesterolemia / Q000178:diet therapy* / Q000235:genetics*; D008071:Lipoprotein Lipase / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010349:Patient Compliance; D016133:Polymerase Chain Reaction; D014280:Triglycerides / Q000032:analysis* / Q000235:genetics
chemical_list: D001054:Apolipoproteins A; C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D006023:Glycoproteins; D014280:Triglycerides; D008071:Lipoprotein Lipase