The aim of this study is to determine whether the promoter polymorphism-203A>C of cholesterol-7α-hydroxylase encoding gene (CYP7A1) affects diurnal variation in CYP7A1 enzyme activity. The methods were as following, test divided into two groups: the study included 16 healthy male volunteers,(1) –8 homozygous for -203A and (2) 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, Measured at intervals of 90 minutes in all experiments. The results were shown: after treatment with cholestyramine and suppressed after treatment with CDCA CYP7A1 activity was up-regulated. 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.
We also analyzed the effect of short-term chenodeoxycholic acid (CDCA) and cholestyramine (a bile acid sequestrant) treatments on CYP7A1 activity throughout the day. These drugs down-regulate and up-regulate CYP7A1 activity, respectively.
In the experment, especially during the Chenodeoxycholic Acid treatment, there were no changes in plasma C4 concentrations on the day of the study in both -203A and -203C allele carriers (P=0.373 and 0.208, respectively). Importantly, no effect of the genotype on the course of C4 concentrations was detected (P=0.221). During the cholestyramine treatment, during the day in -203A allele carriers (P=0.004) C4 concentrations significantly increased. The same phenomenon was also observed in -203C allele carriers (P=0.074), but not significant. However, throughout the day (P=0.659), there is no effect on the course of C4 concentrations in the genotype. Some measures should be adopted and in-depth studies.
