The reabsorption of bile acids regulated by FXR-OATP1A2 is the main factor for the formation of cholesterol gallstone.

The purpose of this study was to demonstrate the aberrant metabolism of bile acids in patients with cholesterol gallstone and explore for its underlying mechanisms.The composition of bile acids collected from the patients with cholelithiasis and the control individuals was analyzed by LC-MS. The expression of genes regulating the metabolism of bile acids were quantitatively determined by real-time PCR or Western blotting. Cholesterol saturation index of patients with gallstone was significantly higher than that of the controls. The concentrations of taurodeoxycholic acid and taurolithocholic acid in the bile of patients were significantly higher than that of the controls. When compared to the controls, it was remarkable in the patients that the mRNA expression of FXR was lower whereas that of OATP1A2 was higher. However, the expressions of both mRNA and protein of CYP8B1 did not differ between the patients and the controls. Although the protein level of CYP8B1 was significantly lower in the subjects with SNP rs3732860(G), the composition of bile acids and the ratio of CA to CDCA remained unaltered in the patients with different SNP genotype of CYP8B1. In conclusion, the axis of FXR-OATP1A2 that physiologically regulated the reabsorption of bile acids might play an important role in the composition of bile acids and the development of gallstone. CYP8B1 gene was irrelevant to the altered composition of bile acids in patients with gallstone.