CYP7A1 A-278C polymorphism affects the response of plasma lipids after dietary cholesterol and cafestol interventions in humans.

The response of plasma lipids to dietary cholesterol and fat varies among individuals. Variations in genes involved in cholesterol metabolism can be important in these interindividual differences. The rate-limiting enzyme in the conversion of cholesterol into bile acids is cholesterol 7-hydroxylase (CYP7A1). We investigated the effect of the A278-C promoter polymorphism in the CYP7A1 gene on responses of plasma lipids to an increased intake in dietary cholesterol (742 ± 114 mg/d), cafestol (57 ± 6 mg/d), saturated fat [change of 8¿9 energy percent/d (en%/d)] and trans fat (change of 10¿11 en%/d) in 496 normolipidemic subjects. These responses were measured in 26 previously published dietary trials. After adjustment for the apolipoprotein E genotype effect, AA-subjects consuming a cholesterol-rich diet had a smaller increase in plasma HDL cholesterol than CC-subjects (0.00 ± 0.02 vs. 0.17 ± 0.04 mmol/L; P <0.001). Upon intake of cafestol, AA-subjects had a smaller increase in plasma total cholesterol than CC-subjects (0.69 ± 0.10 vs. 1.01 ± 0.10 mmol/L; P = 0.028). No effects of the polymorphism were found in the saturated and trans fat interventions. In conclusion, the CYP7A1 polymorphism has a small but significant effect on the increase in plasma HDL cholesterol and plasma total cholesterol after an increased intake of dietary cholesterol and cafestol, respectively