HUMAN APOLIPOPROTEIN-A-I GENE PROMOTER MUTATION INFLUENCES PLASMA LOW-DENSITY-LIPOPROTEIN CHOLESTEROL RESPONSE TO DIETARY-FAT SATURATION

Previous studies have shown that the A to G transition occurring at po sition -75 bp upstream of the transcriptional start site in the human apolipoprotein A-I gene may affect plasma high density lipoprotein cho lesterol (HDL-C) levels and low density lipoprotein cholesterol (LDL-C ) response to changes in amount of dietary fat. We have examined the r esponse 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 monounsaturate d fatty (MUFA) acids (35% fat, 22% MUFA) for 35 days and a diet rich i n polyunsaturated (PUFA) fat (35% fat, 13% PUFA) for 35 days. All meal s were prepared and consumed at the study sites. Lipoproteins were mea sured at the end of each diet period. The allele frequency for the A a llele was 0.13. Subjects carrying the A allele had higher plasma chole sterol, LDL-C and triglyceride levels than those homozygotes for the G allele. As compared to the SAT diet, a PUFA diet induced significantl y 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 pri marily 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 polymor phism (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 chang es in dietary fat saturation specially in women. (C) 1998 Elsevier Sci ence Ireland Ltd. All rights reserved.