AIM: To determine whether the promoter polymorphism -203A>C of cholesterol-7α-hydroxylase encoding gene (CYP7A1) affects diurnal variation in CYP7A1 enzyme activity. METHODS: The study included 16 healthy male volunteers - 8 homozygous for -203A and 8 homozygous for the -203C allele of CYP7A1. Three 15-hour examinations (from 7am to 10pm) were carried out for each of the participants: after one-day treatment with cholestyramine; after one-day treatment with chenodeoxycholic acid (CDCA); and a control examination without any treatment. The plasma concentration of 7α-hydroxy-4-cholesten-3-one (C4), a marker of CYP7A1 activity, was determined in all the experiments at 90-min intervals. RESULTS: CYP7A1 activity was up-regulated after treatment with cholestyramine and suppressed after treatment with CDCA. There were no differences between -203A and -203C allele carriers in the response of enzyme activity to both drugs. In the control experiment, -203A allele carriers displayed diurnal variation in enzyme activity, whereas CYP7A1 activity did not change in -203C allele carriers. These results were confirmed by modeling the dynamics of C4 using polynomial regression. CONCLUSION: The promoter polymorphism of the CYP7A1 gene has a pronounced impact on diurnal variation in CYP7A1 activity.

• MeSH
• Enzyme Activation MeSH
• Cholestenones blood   MeSH
• Cholesterol 7-alpha-Hydroxylase genetics   metabolism   MeSH
• Cholesterol blood   MeSH
• Circadian Rhythm physiology   MeSH
• Adult MeSH
• Humans MeSH
• Area Under Curve MeSH
• Polymorphism, Genetic * MeSH
• Promoter Regions, Genetic MeSH
• Up-Regulation MeSH
• Bile Acids and Salts biosynthesis   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Male MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• 7 alpha-hydroxy-4-cholesten-3-one MeSH Browser
• Cholestenones MeSH
• Cholesterol 7-alpha-Hydroxylase MeSH
• Cholesterol MeSH
• CYP7A1 protein, human MeSH Browser
• Bile Acids and Salts MeSH