Polymorphisms in CYP-7A1, not APOE, influence the change in plasma lipids in response to population dietary change in an 8 year follow-up; results from the Czech MONICA study

Objectives To evaluate the influence of variation in the genes for apolipoprotein E (APOE; ε2, ε3, ε4) and cholesterol-7α hydroxylase (CYP-7A1; –204A→C) on plasma lipid level changes. Design and methods 131 males for whom dietary composition markedly changed and total cholesterol decreased (from 6.21 ± 1.31 mmol/L in 1988 – 5.43 ± 1.06 mmol/L in 1996) over an 8 yr follow-up study. Polymorphisms were investigated using PCR. Results APOE genotype influenced plasma total and LDL cholesterol, with carriers of the ε4 having the highest and ε2 carriers the lowest levels, this reached borderline significance for cholesterol in 1988 (p = 0.06) and strongly affected the 1996 levels of LDL cholesterol (p = 0.008). However, APOE did not influence the change in these measures over time. In contrast, the CYP-7A1 –204A→C polymorphism did not affect lipid measures per se but was strongly associated with a decrease in plasma total cholesterol [AA −0.38 (± 0.20) mmol/L, AC –0.65 ± (0.08), CC –1.33 (± 0.3) mmol/L, p = 0.01] over the 8 yr time period. Conclusions Variation in the CYP-7A1 gene may play an important role in an individual’s sensitivity to dietary composition.