GENETIC-FACTORS AFFECTING THE CONSISTENCY AND MAGNITUDE OF CHANGES INPLASMA-CHOLESTEROL IN RESPONSE TO DIETARY CHALLENGE

We examined the role of common genetic variation in determining the co nsistency and magnitude of change in plasma total cholesterol (TC) lev els in response to two separate changes from a high-saturated (SFA) to a low-saturated/high-polyunsaturated-fat (PUFA) diet, in a group of f ree-living healthy men and women. Consistent responders were defined a s those whose mean difference in the change in TC was within one SD of the mean for all participants, and the remainder were defined as vari able responders. DNA was obtained from 55 individuals and genotype det ermined at the apolipoprotein (ape) B locus (signal peptide, SP), apoC III (C1100-T) and lipoprotein lipase (LPL) gene loci (HindIII). In the 38 consistent responders, the apoBSP24 allele was significantly more common than in the 17 individuals with a variable response (0.29 vs. 0 .12; p<0.05). No other polymorphism showed a significant frequency dif ference between groups. In the group as a whole, the correlation betwe en the change in TC level in response to the first and second dietary change was 0.28 (p=0.05), but those with one or more apoB SP24 alleles and those with the apoCIII genotype CC had a significantly higher cor relation than those with other genotypes (0.46 (p=0.05) vs. 0.12 (NS) and 0.31 (p=0.05) vs. 0.02 (NS), respectively). In the group as a whol e, mean response left TC 10% higher on the SFA than on the PUFA diet, and neither apoB nor apoCIII genotypes affected the magnitude of this response. However, individuals with the LPL HindIII genotype H+H+ had a significantly smaller change in mean TC in response to diet than tho se with one or more H- allele (9.3% vs. 14.4%; p=0.03). Thus variation at the apoB and apoCIII loci affects the consistency of response to c hange in dietary fat content, while variation at the LPL gene locus af fects magnitude of response.