Assessment of cytochrome P450 2E1 activity in Hausa/Fulani of northwest Nigeria using chlorzoxazone as a probe determination of polymorphism

Abstract

Background and objective High expression and activity of cytochrome P450 2E1 have been linked to non-alcoholic fatty liver disease; increased susceptibility to the gastric, nasopharyngeal, colorectal, urinary bladder and esophageal malignancies; and acetaminophen-induced hepatotoxicity. It plays key roles in activating procarcinogens to carcinogens, metabolism of xenobiotics, and hosts of endogenous compounds. This study aimed at determining the polymorphism of this highly polymorphic enzyme among Hausa/Fulani in northwest Nigeria. Materials and methods A total of 20 nonrelated Hausa/Fulani from Sokoto metropolis were selected by convenient sampling. A tablet of 250 mg chlorzoxazone was administered orally to them with 100 ml of distilled water after an overnight fast, and 3 h after dosing, urine was collected. HPLC equipped with a UV detector was performed for simultaneous estimation of chlorzoxazone and its metabolite 6-hydroxychlorzoxazone. Metabolic ratio index method was used for each participant The data generated were analyzed using Statistical Package for the Social Sciences version 20 (SPSS-20) by constructing frequency histogram and probit plots. A trend line was added to the probit plot, and polynomial equation obtained was resolved to get antimode. Participants with antimode greater than or equal to value of intercept on logMR were regarded as poor metabolizers, whereas those with less were extensive metabolizers. Result and conclusion Anti-mode was found to be −1.8, and only 7 of 20 participants were extensive metabolizers (35%, odds 0.54, 95% confidence interval: 0.22–1.3). Although convenience sampling was used, the findings are worrisome considering the highly polymorphic and the procarcinogenic nature of the enzyme.