Objective: The aim of our study was to assess the influence of common promoter polymorphisms in CYP7A1 gene on the ratio of serum 7α-hydroxy-4-cholesten-3-one (cholesten) to cholesterol used for quantification of bile acid malabsorption. Settings: Institute of Clinical Biochemistry and Laboratory Diagnostics, 1st Medical Faculty of the Charles University and General Faculty Hospital; IV. Department of Internal Medicine, General Faculty Hospital, Prague; Center of Experimental Medicine, Institute for Clinical and Experimental Medicine, Prague. Material and Methods: Serum levels of cholesten, a novel marker of bile acid malabsorption, were determined by HPLC in a group of Crohn’s disease (CD) patients with ileal resection (N = 77), inflammation (N = 16), colonic involvement (N = 22), ulcerative colitis (UC) patients (N = 25) and healthy controls (N = 39). Two common polymorphisms in the promoter of CYP7A1 gene encoding cholesterol 7α-monooxygenase, i. e. -203A/C and -469C/T, were analyzed by PCR-RFLP. Results: Serum levels of cholesten corrected to serum cholesterol differed markedly between patients with severe bile acid malabsorption carrying haplotype 203CC/-469TT and -203AA/-469CC (median 13.3 µg/mmol vs. 31.3 µg/mmol, P < 0.01); no significant differences were detected in healthy controls and patients with no or a mild degree of bile acid malabsorption (results expressed as median µg/mmol): healthy controls 2.4 vs. 2.6; ulcerative colitis 3.2 vs. 3.6; Crohn’s colitis 1.3 vs. 3.5 and Crohn’s ileitis 3.8 vs. 12.8. Conclusion: Serum cholesten to cholesterol ratio is influenced by promoter polymorphisms in CYP7A1 gene only in patients with severe bile acid malabsorption.

        Key words: bile acid malabsorption, cholesten, CYP7A1, polymorphism.