Diurnal variation in cholesterol 7α-hydroxylase activity is determined by the -203A>C polymorphism of the CYP7A1 gene.
OBJECTIVE
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.


CONCLUSIONS
The promoter polymorphism of the CYP7A1 gene has a pronounced impact on diurnal variation in CYP7A1 activity.
Miluše
M
Vlachova
Tereza Blahova, Laboratory for Atherosclerosis Research, Institute for Clinical and Experimental Medicine, Vídenska 1958-9, 140 21 Prague 4, Czech Republic, tereza.blahova@ikem.cz.
Tereza
T
Blahova
Vera
V
Lanska
Martin
M
Leníček
Jan
J
Pitha
Libor
L
Vítek
Jan
J
Kovar
D000328:Adult; D019540:Area Under Curve; D001647:Bile Acids and Salts / Q000096:biosynthesis*; D002783:Cholestenones / Q000097:blood; D002784:Cholesterol / Q000097:blood; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology; D004789:Enzyme Activation; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D015854:Up-Regulation
D001647:Bile Acids and Salts; D002783:Cholestenones; C002656:7 alpha-hydroxy-4-cholesten-3-one; D002784:Cholesterol; C553219:CYP7A1 protein, human; D002790:Cholesterol 7-alpha-Hydroxylase