Polymorphism in the coding part of the sterol 12α‐hydroxylase gene does not explain the marked differences in the ratio of cholic acid and chenodeoxycholic acid in human bile

In humans, two primary bile acids are synthesized: cholic acid (CA) and chenodeoxycholic acid (CDCA), the first and rate-limiting enzyme being cholesterol 7alpha-hydroxylase (CYP7A1). CA has one more hydroxyl group at position 12alpha. This hydroxylation is carried out by the sterol 12alpha-hydroxylase (CYP8B1). Earlier, we and others have noticed a marked variation in the ratio between CA and CDCA in human bile. The aim of this study was to investigate whether this marked difference could be due to a genetic polymorphism in the gene of the CYP8B1.Screening for genetic polymorphisms was carried out in a 2.4-kb-long area including the exon and part of the promoter region in subjects who had undergone cholecystectomy earlier, and where bile acid analysis had been performed. Among these subjects those with very high or low CA/CDCA ratios (ranging from 0.9 to 6.8) were investigated. The subjects were all female, normolipidaemic, having normal weight and a normal thyroid function.No polymorphisms were found in the investigated sequence. However, a statistically significant correlation was found between the activity of the CYP7A1 and the ratio between CA and CDCA. The difference in ratio could, at least in part, be explained by the difference in rate of bile acid synthesis.The difference in ratio between CA and CDCA cannot be explained by a polymorphism in the coding area of the CYP8B1.