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Journal of Lipid Research, Vol. 49, 2664-2667, December 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology

Patient-Oriented and Epidemiological Research

CYP7A1 promoter polymorphism –203A>C affects bile salt synthesis rate in patients after ileal resection

Martin Leníek^1,*, Viktor Komárek, Milue Zimolová, Jan Ková, Milan Jirsa^*,, Milan Luká^*, and Libor Vítek^*,**

^* Department of Clinical Biochemistry and Laboratory Diagnostics, 1^st Faculty of Medicine, Charles University in Prague
Inflammatory Bowel Disease Research Center, ISCARE I.V.F. Lighthouse, Prague
Center of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague
^** 4^th Department of Internal Medicine, 1^st Faculty of Medicine, Charles University in Prague

Published, JLR Papers in Press, August 26, 2008.

This work was supported by Grant NR 8963-3 from the Ministry of Health of the Czech Republic.

¹ To whom correspondence should be addressed at Laboratory of Hepatology, UKBLD, U Nemocnice 2, 12808 Prague 2. Phone +420-224962534; fax: +420-224962532; e-mail: mleni{at}centrum.cz

Cholesterol 7-hydroxylase (CYP7A1) plays a crucial role in cholesterol metabolism and has been implicated in genetic susceptibility to atherosclerosis. Thus, an understanding of its transcriptional regulation is of considerable importance. We evaluated the effect of a common –203A>C polymorphism in the CYP7A1 promoter region on the activity of CYP7A1, estimated as the ratios of serum 7-hydroxycholest-4-en-3-one (C4) to either total or non-HDL-cholesterol. The study was performed on patients after resection of the distal ileum, leading to upregulation of CYP7A1 activity (n = 65). Healthy volunteers served as the control group (n = 66). Whereas higher CYP7A1 activity was associated with the –203A allele in the patient group (C4/cholesterol ratio, 29.0 vs. 14.8 µg/mmol, P = 0.032; C4/non-HDL-cholesterol ratio, 53.3 vs. 21.3 µg/mmol in –203AA and –203CC, P = 0.017, respectively), no differences were observed in the healthy controls. We conclude that under physiological conditions, the –203A>C polymorphism in the CYP7A1 gene promoter region does not seem to have any clinically relevant effect. However, in patients with severe bile salt malabsorption, this polymorphism markedly affects CYP7A1 activity.

Supplementary key words bile salt malabsorption • cholesterol • atherosclerosis • bile acid • metabolism

Abbreviations: BS, bile salt; CYP7A1, cholesterol 7-hydroxylase; C4, 7-hydroxycholest-4-en-3-one

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