Review
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 21, 2019; 25(23): 2846-2862
Published online Jun 21, 2019. doi: 10.3748/wjg.v25.i23.2846
Role of cytochrome P450 polymorphisms and functions in development of ulcerative colitis
Alaattin Sen, Holger Stark
Alaattin Sen, Department of Molecular Biology and Genetics, Faculty of Life and Natural Sciences, Abdullah Gul University, Kayseri 38080, Turkey
Alaattin Sen, Biology Department, Faculty of Arts and Sciences, Pamukkale University, Denizli 20070, Turkey
Holger Stark, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, Duesseldorf 40225, Germany
Author contributions: Sen A conceptualized and designed the review; Stark H drafted the initial manuscript; all authors reviewed and approved the final manuscript as submitted.
Conflict-of-interest statement: Authors declare no conflict of interest.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Alaattin Sen, PhD, Academic Fellow, Academic Research, Chairman, Full Professor, Instructor, Professor, Research Scientist, Senior Lecturer, Senior Researcher, Senior Scientist, Department of Molecular Biology and Genetics, Faculty of Life and Natural Sciences, Abdullah Gul University, Sumer Campus, Kocasinan, Kayseri 38080, Turkey. sena@pau.edu.tr
Telephone: +90-352-2248800 Fax: +90-352-3388828
Received: March 20, 2019
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
Processing time: 93 Days and 9.7 Hours
Abstract

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.

Keywords: Cytochrome P450; Polymorphism; Function; Ulcerative colitis; Aetiology

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.