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

Journal of Lipid Research
Martin LenícekLibor Vítek

Abstract

Cholesterol 7alpha-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 7alpha-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 microg/mmol, P = 0.032; C4/non-HDL-cholesterol ratio, 53.3 vs. 21.3 microg/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.

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Citations

Nov 9, 2010·Inflammatory Bowel Diseases·Martin LenicekLibor Vitek
Nov 15, 2011·Journal of Cardiovascular Pharmacology·Jian ShenJosé M Ordovás
Sep 10, 2011·Basic & Clinical Pharmacology & Toxicology·Xiaoqiang XiangMikko Niemi
May 19, 2009·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·A L V BarcelosC M D Silva
Oct 31, 2019·Journal of Cardiovascular Pharmacology·Na LiuMan Zhang
Jul 23, 2021·Liver Research·John Y L Chiang, Jessica M Ferrell

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