Genetic variation in the farnesoid X-receptor predicts Crohn's disease severity in female patients.

ABSTRACT: The farnesoid X receptor (FXR) is implicated in Crohn's disease (CD) pathogenesis. It is unclear how genetic variation in FXR impacts CD severity versus genetic variation in nuclear receptors such as pregnane X receptor (PXR) and the multi-drug resistance protein 1 (MDR1, ABCB1). To evaluate FXR-1G?>?T as a genomic biomarker of severity in CD and propose a plausible molecular mechanism. A retrospective study (n?=?542) was conducted in a Canadian cohort of CD patients. Genotypic analysis (FXR-1G?>?T, MDR1 3435C?>?T and PXR -25385C?>?T) as well as determination of the FXR downstream product, fibroblast growth factor (FGF) 19 was performed. Primary outcomes included risk and time to first CD-related surgery. The effect of estrogen on wild type and variant FXR activity was assessed in HepG2 cells. The FXR-1GT genotype was associated with the risk of (odds ratio, OR?=?3.34, 95% CI?=?1.58-7.05, p?=?0.002) and earlier progression to surgery (hazard ratio, HR?=?3.00, 95% CI?=?1.86-4.83, p?

SUBMITTER: Wilson A 

PROVIDER: S-EPMC7366697 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature