title: CYP7A1 A-278C polymorphism affects the response of plasma lipids after dietary cholesterol or cafestol interventions in humans.
abstract: 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 7alpha-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.
authors.affiliation: TNO Prevention and Health, Gaubius Laboratory, Leiden, The Netherlands.
authors.forename: Maaike K
authors.initials: MK
authors.lastname: Hofman
authors.forename: Rianne M
authors.initials: RM
authors.lastname: Weggemans
authors.forename: Peter L
authors.initials: PL
authors.lastname: Zock
authors.forename: Evert G
authors.initials: EG
authors.lastname: Schouten
authors.forename: Martijn B
authors.initials: MB
authors.lastname: Katan
authors.forename: Hans M G
authors.initials: HM
authors.lastname: Princen
mesh_terms: D000225:Adenine; D000483:Alleles; D002784:Cholesterol / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D002791:Cholesterol, Dietary / Q000008:administration & dosage / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood; D018849:Controlled Clinical Trials as Topic; D003596:Cytosine; D004224:Diterpenes / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006720:Homozygote; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D011110:Polymorphism, Genetic / Q000502:physiology*; D011401:Promoter Regions, Genetic
chemical_list: D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D004224:Diterpenes; D008055:Lipids; D003596:Cytosine; D002784:Cholesterol; C053400:cafestol; D002790:Cholesterol 7-alpha-Hydroxylase; D000225:Adenine