%0 Journal Article %A Jie Liu %A Julia Yue Cui %A Yuan-Fu Lu %A J. Christopher Corton %A Curtis D. Klaassen %T Sex-, age-, and race/ethnicity-dependent variations in drug-processing and NRF2-regulated genes in human livers %D 2020 %R 10.1124/dmd.120.000181 %J Drug Metabolism and Disposition %P DMD-AR-2020-000181 %X Individual variations in xenobiotic metabolism affect the sensitivity to diseases. In this study, the impacts of sex, age and race/ethnicity on drug-processing genes and NRF2 genes in human livers were examined via QuantiGene multiplex suspension array (226 samples) and qPCR (247 samples) to profile the expression of nuclear receptors, cytochrome P450s, conjugation enzymes, transporters, bile acid metabolism and NRF2-regulated genes. Sex differences were found in expression of about half of the genes, but in general the differences were not large. For example, females had higher transcript levels of CAT, GCLC, HO-1, KEAP1, SOD1, and TXNRD1 compared to males via qPCR. There were no apparent differences due to age except children had higher GCLM and elderly had higher MRP3. African Americans had lower expression of FXR but higher expression of HO-1, Caucasians had higher expression of OAT2, and Hispanics had higher expression of FXR, SULT2A1, SHP, and BSEP. An examination of 34 diseased and control human liver samples showed that compared to disease-free livers, fibrotic livers had higher NQO1, GCLC, GCLM and NRF2; hepatocellular carcinoma had higher transcript levels of NQO1 and KEAP1, and steatotic livers had lower GCLC, GCLM and HO-1 expression. In summary, in drug-processing gene and NRF2 genes, sex differences were the major findings, and there were no apparent age-differences and race/ethnicity differences occurred for a few genes. These descriptive findings could add to our understanding of the sex-, age-, and race/ethnicity -dependent differences in drug-processing genes, as well as NRF2 genes in normal and diseased human livers. Significance Statement Significance statement In human liver drug-processing and NRF2 genes, sex differences were the main finding. There were no apparent differences due to age, except children had higher GCLM and elderly had higher MRP3. African Americans had lower expression of FXR but higher expression of HO-1, Caucasians had higher expression of OAT2, and Hispanics had higher expression of FXR, SHP, SULT2A1 and BSEP. %U https://dmd.aspetjournals.org/content/dmd/early/2020/11/08/dmd.120.000181.full.pdf