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Nutrient-Gene Interactions

CYP7A1 A-278C Polymorphism Affects the Response of Plasma Lipids after Dietary Cholesterol or Cafestol Interventions in Humans^1,2

Maaike K. Hofman^*,, Rianne M. Weggemans^**, Peter L. Zock, Evert G. Schouten, Martijn B. Katan^**, and Hans M. G. Princen^*,3

^* TNO Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands; Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; ^** Unilever Health Institute, Unilever Research and Development, Vlaardingen, The Netherlands; and Wageningen Centre for Food Sciences, Wageningen, The Netherlands

³To whom correspondence should be addressed. E-mail: jmg.princen{at}pg.tno.nl.

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.

KEY WORDS: • CYP7A1 • polymorphism • cholesterol • cafestol • dietary interventions

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