Targeting FXR with small molecules has been exploited to treat lipid-related disorders and diseases such as cholestasis, gallstones and hepatic disorders.
Sequencing of the FXR gene was conducted in a randomly selected cohort of gallstone carriers (n=30) and control subjects (n=16) from Stuttgart, Germany.
In contrast, NR1H4_1 displayed no association with gallstone prevalence in a German population, whereas in a Chilean population we observed a trend towards a protective effect of NR1H4_1.
These findings suggest that PGC-1 can play a role in the prevention of cholesterol gallstone disease in humans; this might take place via interaction with the bile acid receptor FXR, whose protective role in cholelithiasis has been suggested by recent evidence in animal models and other coactivators.