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

Martin Lenicek, Viktor Komarek, Miluse Zimolova, Jan Kovar, Milan Jirsa, Milan Lukas, and Libor Vitek

Department of Clinical Biochemistry and Laboratory Diagnostics, 1st Faculty of Medicine, Charles University of Prague, Prague 12808

Corresponding Author: mleni{at}centrum.cz

Cholesterol 7 $alpha$ -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 $alpha$ -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 $mu$ g/mmol, p=0.032; C4/non-HDL cholesterol ratio: 53.3 vs. 21.3 $mu$ g/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 (BS) malabsorption this polymorphism markedly affects CYP7A1 activity.

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