Farnesoid x receptor in human metabolism and disease: the interplay between gene polymorphisms, clinical phenotypes and disease susceptibility

Farnesoid x receptor (FXR) belongs to the group of nuclear receptors (NRs), which regulate the expression of various genes by binding to DNA either as a monomer or a heterodimer with retinoid x receptor.FXR affects several metabolic pathways through its specific target genes, regulating bile acid (BA) synthesis and homeostasis, glucose and lipid metabolism, also exhibiting a crucial role in intestinal bacterial growth and liver regeneration. Additionally, FXR is involved in the pathogenesis of different cholestatic diseases, as well as non-alcoholic fatty liver disease, inflammatory bowel disease (IBD) and primary idiopathic BA malabsorption.Analyses of certain FXR polymorphisms revealed associations with clinical phenotypes and susceptibility to various human diseases. FXR single-nucleotide polymorphisms seem to be correlated with differences in glucose homeostasis, gallstone formation, intrahepatic cholestasis of pregnancy, IBD and therapeutic response to hypolipidemic therapy, among studied populations. Unfortunately, little data are still available and more studies remain to be done to determine the contribution of FXR polymorphisms in estimating risk factors and clinical outcomes for several diseases.