Genetic factors affecting the consistency and magnitude of changes in plasma cholesterol in response to dietary challenge

We examined the role of common genetic variation in determining theconsistency and magnitude of change in plasma total cholesterol (TC) levelsin response to two separate changes from a high-saturated (SFA) to alow-saturated/high-polyunsaturated-fat (PUFA) diet, in a group offree-living healthy men and women. Consistent responders were defined asthose whose mean difference in the change in TC was within one SD of themean for all participants, and the remainder were defined as variableresponders. DNA was obtained from 55 individuals and genotype determined atthe apolipoprotein (apo) B locus (signal peptide, SP), apoCIII (C1100-T)and lipoprotein lipase (LPL) gene loci (HindIII). In the 38 consistentresponders, the apoBSP24 allele was significantly more common than in the17 individuals with a variable response (0.29 vs. 0.12; p < 0.05). Noother polymorphism showed a significant frequency difference betweengroups. In the group as a whole, the correlation between the change in TClevel 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 theapoCIII genotype CC had a significantly higher correlation than those withother 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 whole, mean response left TC 10%higher on the SFA than on the PUFA diet, and neither apoB nor apoCIIIgenotypes affected the magnitude of this response. However, individualswith the LPL HindIII genotype H+ H+ had a significantly smaller change inmean TC in response to diet than those with one or more H- allele (9.3% vs.14.4%; p = 0.03). Thus variation at the apoB and apoCIII loci affects theconsistency of response to change in dietary fat content, while variationat the LPL gene locus affects magnitude of response.