Published online Jun 21, 2019. doi: 10.3748/wjg.v25.i23.2846
Peer-review started: March 20, 2019
First decision: April 5, 2019
Revised: April 26, 2019
Accepted: May 8, 2019
Article in press: May 8, 2019
Published online: June 21, 2019
Cytochromes P450s (CYPs) are terminal enzymes in CYP dependent monooxygenases, which constitute a superfamily of enzymes catalysing the metabolism of both endogenous and exogenous substances. One of their main tasks is to facilitate the excretion of these substances and eliminate their toxicities in most phase 1 reactions. Endogenous substrates of CYPs include steroids, bile acids, eicosanoids, cholesterol, vitamin D and neurotransmitters. About 80% of currently used drugs and environmental chemicals comprise exogenous substrates for CYPs. Genetic polymorphisms of CYPs may affect the enzyme functions and have been reported to be associated with various diseases and adverse drug reactions among different populations. In this review, we discuss the role of some critical CYP isoforms (CYP1A1, CYP2D6, CYP2J2, CYP2R1, CYP3A5, CYP3A7, CYP4F3, CYP24A1, CYP26B1 and CYP27B1) in the pathogenesis or aetiology of ulcerative colitis concerning gene polymorphisms. In addition, their significance in metabolism concerning ulcerative colitis in patients is also discussed showing a clear underestimation in genetic studies performed so far.
Core tip: The role of cytochrome P450s (CYPs) genes in the pathogenesis of ulcerative colitis (UC). Extrahepatic and extrarenal CYPs (e.g., macrophages and dendritic cells of colonic mucosa) have a critical role in UC development. Polymorphisms discussed can result in dysregulation of these enzymes in favour of alternative pathways producing more reactive metabolites. Production of reactive metabolites is favouring more severe disease states. Pharmacogenetics might facilitate individualized medicine for UC in the future although actually available data is limited.