Diurnal variation in cholesterol 7 alpha-hydroxylase activity is determined by the-203A > C polymorphism of the CYP7A1 gene
Abstract
Aim To determine whether the promoter polymorphism -203A>C of cholesterol-7 alpha-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 7 alpha-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.