Genetic factors affecting the consistency and magnitude of changes in plasma cholesterol in response to dietary challenge |
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Authors: | Humphries SE; Talmud PJ; Cox C; Sutherland W; Mann J |
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Institution: | Department of Medicine, UCL Medical School, London, UK. |
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Abstract: | We examined the role of common genetic variation in determining the
consistency and magnitude of change in plasma total cholesterol (TC) levels
in response to two separate changes from a high-saturated (SFA) to a
low-saturated/high-polyunsaturated-fat (PUFA) diet, in a group of
free-living healthy men and women. Consistent responders were defined as
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 variable
responders. DNA was obtained from 55 individuals and genotype determined at
the apolipoprotein (apo) B locus (signal peptide, SP), apoCIII (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 difference between
groups. In the group as a whole, the correlation between 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 correlation 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 whole, 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 those 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 change in dietary fat content, while variation
at the LPL gene locus affects magnitude of response.
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