title: Human apolipoprotein A-I gene promoter mutation influences plasma low density lipoprotein cholesterol response to dietary fat saturation.
abstract: Previous studies have shown that the A to G transition occurring at position -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cholesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C) response to changes in amount of dietary fat. We have examined the response to dietary fat saturation as a function of this mutation in 50 men and women. Subjects were first fed a saturated (SAT) fat diet (35% fat, 17% SAT) for 28 days, followed by a diet rich in monounsaturated fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich in polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meals were prepared and consumed at the study sites. Lipoproteins were measured at the end of each diet period. The allele frequency for the A allele was 0.13. Subjects carrying the A allele had higher plasma cholesterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantly greater plasma total (P = 0.003) and LDL-C decreases (P = 0.001) in G/A women (-1.62 and -1.32 mmol/l, respectively) than in G/G subjects (-0.87 and -0.74 mmol/l for plasma and LDL-C, respectively). Multiple regression analysis demonstrated that in women, the variability in LDL-C response from a diet rich in SAT fat to a diet rich in PUFA was primarily due to LDL-C levels (during the SAT phase), accounting for 55.1% of the variance, waist to hip ratio (W/H; 11.4%) and the G/A polymorphism (10%). Whereas in men the major determinant of this response was smoking (21.4%). In conclusion, the G/A polymorphism appears to have a small but significant effect on plasma LDL-C responsiveness to changes in dietary fat saturation specially in women.
authors.affiliation: Fundacion Jimenez Diaz, Madrid, Spain.
authors.forename: P
authors.initials: P
authors.lastname: Mata
authors.forename: J
authors.initials: J
authors.lastname: Lopez-Miranda
authors.forename: M
authors.initials: M
authors.lastname: Pocovi
authors.forename: R
authors.initials: R
authors.lastname: Alonso
authors.forename: C
authors.initials: C
authors.lastname: Lahoz
authors.forename: C
authors.initials: C
authors.lastname: Marin
authors.forename: C
authors.initials: C
authors.lastname: Garces
authors.forename: A
authors.initials: A
authors.lastname: Cenarro
authors.forename: F
authors.initials: F
authors.lastname: Perez-Jimenez
authors.forename: M
authors.initials: M
authors.lastname: de Oya
authors.forename: J M
authors.initials: JM
authors.lastname: Ordovas
mesh_terms: D000328:Adult; D016632:Apolipoprotein A-I / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood*; D004247:DNA / Q000032:analysis; D017931:DNA Primers / Q000737:chemistry; D004041:Dietary Fats / Q000008:administration & dosage*; D005229:Fatty Acids, Monounsaturated / Q000008:administration & dosage; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000178:diet therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D019518:Postprandial Period; D011401:Promoter Regions, Genetic / Q000235:genetics*; D014280:Triglycerides / Q000097:blood
chemical_list: D016632:Apolipoprotein A-I; D008078:Cholesterol, LDL; D017931:DNA Primers; D004041:Dietary Fats; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D014280:Triglycerides; D004247:DNA