Izvorni znanstveni članak
https://doi.org/10.3325/cmj.2016.57.111
Diurnal variation in cholesterol 7α-hydroxylase activity is determined by the -203A>C polymorphism of the CYP7A1 gene
Miluše Vlachová
; Institute for Clinical and Experimental Medicine, Prague Czech Republic
Tereza Blahová
; Institute for Clinical and Experimental Medicine, Prague Czech Republic
Věra Lánská
; Institute for Clinical and Experimental Medicine, Prague Czech Republic
Martin Leníček
; Institute of Clinical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine, CharlesUniversity in Prague, Prague, Czech Republic
Jan Piťha
; Institute for Clinical and Experimental Medicine, Prague Czech Republic
Libor Vítek
; Institute of Clinical Biochemistry and Laboratory Diagnostics 1st Faculty of Medicine, CharlesUniversity in Prague, Prague, Czech Republic
Jan Kovář
; Institute for Clinical and Experimental Medicine, Prague Czech Republic
Sažetak
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.
Ključne riječi
Hrčak ID:
169471
URI
Datum izdavanja:
15.4.2016.
Posjeta: 883 *