Expression of cytochrome P450 isozyme transcripts and activities in human livers
Creators: name: Liu, Jie
name: Lu, Yuan-Fu
name: Corton, J. Christopher
name: Klaassen, Curtis D.
Publisher: name: Taylor & Francis
Year: 2020
Subjects: subject: Biochemistry
subject: Genetics
subject: FOS: Biological sciences
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Science Policy
subject: Sociology
subject: FOS: Sociology
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Inorganic Chemistry
subject: FOS: Chemical sciences
subject: Virology

description: Individual differences in cytochrome P450 (CYP) enzymes contribute to responses to drugs and environmental chemicals. The expression of CYPs is influenced by sex, age, and ethnicity. Human CYP studies are often conducted with human liver microsomes and liver cells to evaluate chemical induction and drug interactions. However, the basal or constitutive expression of CYP transcripts and enzyme activities in the intact liver are also important in our understanding of individual variation in CYPs.This study utilised 100 human liver samples to profile the constitutive expression of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, and 4A11 enzyme activity and transcript levels. The mRNA expression of the CYPs and xenobiotic receptors <i>AhR</i>, <i>CAR</i>, and <i>PXR</i> was examined <i>via</i> qPCR.Results showed that there was greater inter-individual variation in mRNA expression than in enzyme activities, except for CYP2C19. Females had higher CYP3A4 activity than males. Children had lower CYP4A14 activity, while elderly had lower P450 oxidoreductase activity. Compared to Caucasians, Hispanics had higher CYP2C8 activity and higher <i>CYP2B6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> mRNA expression, whereas African Americans had lower CYP2D6 mRNA expression.These results add to our understanding of individual variations in xenobiotic metabolism and toxicology. Individual differences in cytochrome P450 (CYP) enzymes contribute to responses to drugs and environmental chemicals. The expression of CYPs is influenced by sex, age, and ethnicity. Human CYP studies are often conducted with human liver microsomes and liver cells to evaluate chemical induction and drug interactions. However, the basal or constitutive expression of CYP transcripts and enzyme activities in the intact liver are also important in our understanding of individual variation in CYPs. This study utilised 100 human liver samples to profile the constitutive expression of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 3A4, and 4A11 enzyme activity and transcript levels. The mRNA expression of the CYPs and xenobiotic receptors <i>AhR</i>, <i>CAR</i>, and <i>PXR</i> was examined <i>via</i> qPCR. Results showed that there was greater inter-individual variation in mRNA expression than in enzyme activities, except for CYP2C19. Females had higher CYP3A4 activity than males. Children had lower CYP4A14 activity, while elderly had lower P450 oxidoreductase activity. Compared to Caucasians, Hispanics had higher CYP2C8 activity and higher <i>CYP2B6</i>, <i>CYP2C9</i>, and <i>CYP2C19</i> mRNA expression, whereas African Americans had lower CYP2D6 mRNA expression. These results add to our understanding of individual variations in xenobiotic metabolism and toxicology.