Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Single nucleotide polymorphisms (SNPs) in genes encoding drug-metabolizing enzymes, transporters, receptors, and other drug targets have been widely implicated as contributors to differences among individuals as regards the efficacy and toxicity of many medications, as well as the susceptibility to complex diseases. By combining the polymerase chain reaction (PCR) technique with direct sequencing, we screened genomic DNAs from 48 Japanese volunteers for SNPs in genes encoding three quinone oxidoreductases (NQO1, NQO2, and PIG3) and 17 sulfotransferases (SULT1A1, SULT1A2, SULT1A3, SULT1C1, SULT1C2, SULT2A1, SULT2B1, ST1B2, TPST1, TPST2, SULTX3, STE, CST, HNK-1 ST, CHST2, CHST4, and CHST5). In all, we identified 320 SNPs from these 20 loci: 22 within coding elements, 21 in 5' flanking regions, 10 in 5' untranslated regions, 223 in introns, 19 in 3' untranslated regions, and 25 in 3' flanking regions. The ratio of transitions to transversions was approximately 2.3 to 1. Of the 22 coding SNPs, 6 were nonsynonymous substitutions that resulted in amino-acid substitutions. The high-density SNP maps we constructed from this data for each of the quinone oxidoreductases and sulfotransferases examined here should provide useful information for investigations designed to detect association(s) between genetic variations and common diseases or responsiveness to drug therapy.
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PMID:Catalog of 320 single nucleotide polymorphisms (SNPs) in 20 quinone oxidoreductase and sulfotransferase genes. 1132 64

Metabolic activation of 17beta-estradiol (E2) to catechols and quinones together with lack of deactivation constitute risk factors in human breast carcinogenesis. E2-catchols are generated by cytochrome P450-dependent monooxygenases (CYPs). Deactivation of E2, E2-catechols, and E2-quinones is mediated by UDP-glucuronosyltransferase (UGT), sulfotransferase (SULT), catechol-O-methyltransferase (COMT), glutathione-S-transferase (GST), and NADPH-quinone-oxidoreductase (QR) isozymes, respectively. The aim of the present study was to quantify mRNA levels of E2-metabolizing isozymes expressed in MCF-7 cells cultured in the presence/absence of steroids by reverse transcription/competitive PCR in relation to the housekeeping gene hypoxanthine-guanine phosphoribosyltransferase and compare them with expression levels in normal human mammary gland (MG) and liver tissue. CYP1A1, 1B1, SULT1A1, 1A2, membrane-bound and soluble COMT, GSTT1, QR1, and UGT2B7 were detected in both tissues and MCF-7 cells; however, most enzymes were expressed at least tenfold higher in liver. Yet, CYP1B1 was expressed as high in breast as in liver and UGTs were not detected in MCF-7 cells cultured with steroids. MCF-7 cells cultured steroid-free additionally expressed CYP1A2 as well as UGT1A4, 1A8, and 1A9. Normal human liver but not MG expressed CYP1A2, 3A4, UGT1A1, 1A3, 1A4, 1A9, and SULT2A1. UGT1A8 was only detected in MCF7 cells but was not found in human liver. Thus, our study provides a comprehensive overview of expression levels of E2-metabolizing enzymes in a popular in vitro model and in human tissues, which will contribute to the interpretation of in vitro studies concerning the activation/deactivation of E2.
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PMID:Gene expression of 17beta-estradiol-metabolizing isozymes: comparison of normal human mammary gland to normal human liver and to cultured human breast adenocarcinoma cells. 1849 89

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.
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PMID:Sex-, age-, and race/ethnicity-dependent variations in drug-processing and NRF2-regulated genes in human livers. 3316 98