PT - JOURNAL ARTICLE AU - Hai-Feng Zhang AU - Zhi-Hui Li AU - Jia-Yu Liu AU - Ting-Ting Liu AU - Ping Wang AU - Yan Fang AU - Jun Zhou AU - Ming-Zhu Cui AU - Na Gao AU - Xin Tian AU - Jie Gao AU - Qiang: Wen AU - Lin-Jing Jia AU - Hai-Ling Qiao TI - Correlation of cytochrome P450 oxidoreductase expression with the expression of 10 isoforms of cytochrome P450 in human liver AID - 10.1124/dmd.116.069849 DP - 2016 Jan 01 TA - Drug Metabolism and Disposition PG - dmd.116.069849 4099 - http://dmd.aspetjournals.org/content/early/2016/06/06/dmd.116.069849.short 4100 - http://dmd.aspetjournals.org/content/early/2016/06/06/dmd.116.069849.full AB - Human cytochrome P450 oxidoreductase (POR) provides electrons for all microsomal cytochromes P450 (CYP) and plays an indispensable role in drug metabolism catalyzed by this family of enzymes. We evaluated 100 human liver samples and found that POR protein content varied 13-fold, from 12.59 to 160.97 pmol/mg, with a median value of 67.99 pmol/mg; POR mRNA expression varied by 26.4-fold. POR activity was less variable with a median value of 56.05 nmol/min/mg. Cigarette smoking and alcohol consumption clearly influenced POR activity. Liver samples with a 2286822 TT genotype had significantly higher POR mRNA expression than samples with CT genotype. Homozygous carriers of POR2286822 C>T, 2286823 G>A, and 3823884 A>C had significantly lower POR protein levels compared with the corresponding heterozygous carriers. Liver samples from individuals homozygous at 286823G>A, 1135612 A>G, and 10954732 G>A generally had lower POR activity levels than those from heterozygous or wild-type samples, whereas the common variant POR*28 significantly increased POR activity. There was a strong association between POR and the expression of all 10 CYP isoforms at the mRNA and protein level, whereas the relationship at the activity level, as well as the effect of POR protein content on CYP activity, was less pronounced. POR transcription was strongly correlated with both HNF4α and PXR mRNA levels. In conclusion, we have elucidated some potentially important correlations between POR SNPs and POR expression in the Chinese population and have developed a database that correlates POR expression with the expression and activity of 10 CYPs important in drug metabolism.