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)

This paper lists the genotype frequencies of 50 polymorphisms of 37 genes (ALDH2, ADRB2, ADRB3, COMT, CD36, CXCR2, CCND1, COX2, CYP2A6, CYP17, CYP19, IGF1, IL-1A, IL-1B, IL-1RN, IL-1R1, IL-6, IL-8, IL-10, LEP, Le, L-myc, MPO, MTR, MTHFR, MAO-A, NQO1, OGG1, p53, p73, Se, SRD5A2, TGF-B, TNF-A, TNF-B, XPD, and XRCC1) and 6 sets of combined genotype frequencies for 241 non-cancer Japanese outpatients. Though the genotype frequencies of 25 polymorphisms have already been reported in our previous papers, 15 polymorphisms (CD36 A52C, CXCR2 C785T, CCND1 G870A, IGF1 C/T at intron 2 and G2502T, IL-1A 46-bp VNTR, IL-1R1 C-116T, IL-6 Ins/Del 17C, IL-8 A-278T and C74T, IL- 10 T-819C, LEP A-2548G, SRD5A2 2-bp VNTR, XPD Lys751Gln, and XRCC1 Arg399Gln) and six sets of combined genotype frequencies (IL-1B C-31T and IL-1A C-889T, IL-1B C-31T and IL-1RN 86-bp VNTR, IL-1B C-31T and IL-1R1 C-116T, TNF-A G-308A and TNF-B A252G, SRD5A2 Val89Leu and 2-bp VNTR, and XRCC1 Arg399Gln and XPD Lys751Gln) were reported in this paper for the first time for Japanese. Although microarray technology will produce this kind of information in near future, this is the first document that reports the genotype/allele frequencies among Japanese for an archival purpose.
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PMID:Genotype frequencies of 50 polymorphisms for 241 Japanese non-cancer patients. 1216 25

Susceptibility to colorectal cancer, one of the most common forms of cancer in the Western world, has been associated with several environmental and dietary risk factors. Dietary exposure to food derived heterocyclic amine carcinogens and polycyclic aromatic hydrocarbons have been proposed as specific risk factors. Many polymorphic Phase I and Phase II drug metabolizing enzymes are responsible for the metabolism and disposition of these compounds and it is therefore possible that inheritance of specific allelic variants of these enzymes may influence colorectal cancer susceptibility. In a multicenter case-control study, 490 colorectal cancer patients and 593 controls (433 matched case-control pairs) were genotyped for common polymorphisms in the cytochrome P450 (CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2C9, CYP2C19 and CYP2D6), glutathione S-transferase (GSTM1, GSTP1 and GSTT1), sulfotransferase (SULT1A1 and SULT1A2), N-acetyl transferase 2 (NAT2), NAD(P)H:quinone oxidoreductase (NQO1), methylenetetrahydrofolate reductase (MTHFR), and microsomal epoxide hydrolase (EPHX1) genes. Matched case-control analysis identified alleles associated with higher colorectal cancer risk as carriage of CYP1A1*2C (OR = 2.15, 95% CI 1.36-3.39) and homozygosity for GSTM1*2/*2 (OR = 1.53, 95% CI 1.16-2.02). In contrast, inheritance of the CYP2A6*2 (OR = 0.51, 95% CI 0.28-1.06), CYP2C19*2 (OR = 0.72, 95% CI 0.52-0.98) and the EPHX1(His113) alleles were associated with reduced cancer risk. We found no association with colorectal cancer risk with NAT2 genotype or any of the other polymorphic genes associated with the metabolism and disposition of heterocyclic amine carcinogens. This data suggests that heterocyclic amines do not play an important role in the aetiology of colorectal cancer but that exposure to other carcinogens such as polycyclic aromatic hydrocarbons may be important determinants of cancer risk.
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PMID:A pharmacogenetic study to investigate the role of dietary carcinogens in the etiology of colorectal cancer. 1241 32

We present an oligonucleotide microarray ("MetaboChip") based on the arrayed primer extension (APEX) technique, allowing genotyping of single nucleotide polymorphisms (SNPs) in genes of interest for cancer susceptibility and pharmacogenetics. APEX consists of a sequencing reaction primed by an oligonucleotide anchored with its 5' end to a glass slide and terminating one nucleotide before the polymorphic site. The extension with one fluorescently labeled dideoxynucleotide complementary to the template reveals the polymorphism. Ninety-three SNPs in 42 genes were selected among those resequenced in the context of the SNP500 project, using a set of 102 reference DNA samples from the Coriell Biorepository. Selected SNPs belong to the following genes: ADH1B, ALDH2, APEX, CDKN2A, COMT, CYP1A1, CYP1A2, CYP1B1, CYP2A6, CYP2C19, CYP2C9, CYP2E1, CYP3A4, DRD2, DRD4, EPHX1, ERCC1, ERCC2, ERCC4, ERCC5, GRPR, GSTA4, GSTM3, GSTP1, GSTT2, LIG3, MDM2, MGMT, MPO, NAT1, NAT2, NQO1, OGG1, PCNA, POLB, SLC6A3, SOD2, TP53, XRCC1, XRCC2, XRCC3, and XRCC9. We assessed the performance of APEX by comparing the results obtained with MetaboChip against those reported by the SNP500. Among 88 SNPs that yielded signals, 6 showed less than 99% of concordance, whereas 82 performed accurately, showing that APEX is a reliable and sensitive genotyping method.
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PMID:Evaluation of a microarray for genotyping polymorphisms related to xenobiotic metabolism and DNA repair. 1457 48

Binding and activation of the aryl hydrocarbon receptor (AhR) is thought to be an essential step in the toxicity of the environmental pollutants dioxins and dioxin-like PCBs. However, also a number of natural compounds, referred to as NAhRAs (natural Ah-receptor agonists), which are present in, for example, fruits and vegetables, can bind and activate this receptor. To study their potential effects in humans, we first investigated the effect of the prototypical AhR agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on gene expression in ex vivo exposed freshly isolated human lymphocytes, and compared the resulting gene expression profile with those caused by the well-known NAhRA indolo[3,2-b]carbazole (ICZ), originating from cruciferous vegetables, and by a hexane extract of NAhRA-containing grapefruit juice (GJE). Only ICZ induced a gene expression profile similar to TCDD in the lymphocytes, and both significantly up-regulated CYP1B1 and TIPARP (TCDD-inducible poly (ADP-ribose) polymerase) mRNA. Next, we performed a human intervention study with NAhRA-containing cruciferous vegetables and grapefruit juice. The expression of the prototypical AhR-responsive genes CYP1A1, CYP1B1 and NQO1 in whole blood cells and in freshly isolated lymphocytes was not significantly affected. Also enzyme activities of CYP1A2, CYP2A6, N-acetyltransferase 2 (NAT2) and xanthine oxidase (XO), as judged by caffeine metabolites in urine, were unaffected, except for a small down-regulation of NAT2 activity by grapefruit juice. Examination of blood plasma with DR CALUX showed a 12% increased AhR agonist activity 3 and 24 h after consumption of cruciferous vegetables, but did not show a significant effect of grapefruit juice consumption. We conclude that intake of NAhRAs from food may result in minor AhR-related effects measurable in human blood and urine.
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PMID:A human intervention study with foods containing natural Ah-receptor agonists does not significantly show AhR-mediated effects as measured in blood cells and urine. 1876 78

A substantial part of the interindividual variability in response to drugs and xenobiotics is related to genetically-determined impairment in drug metabolism. Several drug-metabolising enzymes are polymorphic in humans and often polymorphisms are strongly related to altered drug biodisposition and to the risk of developing adverse effects. Drugs used in general anaesthesia undergo polymorphic metabolism. Among these, halothane is metabolized by cytochrome P450 (CYP) 2E1 and, to a lesser extent, by CYP3A4 and CYP2A6. CYP2E1 also plays a key role in the metabolism of isoflurane, sevoflurane, enflurane and desflurane. CYP2B6, CYP3A4 and CYP2C9 play a relevant role in the metabolism of ketamine. The enzymes involved in the metabolism of thiopental and etomidate remains to be elucidated. Propofol is metabolized mainly by glucuronidation by uridine diphosphate-glucuronosyltransferases (UGTs) and by hydroxylation by CYP2B6 and CYP2C enzymes. The enzymes SULT1A1 and NQO1 participate in later steps in propofol metabolism. All the above-mentioned anaesthetic-metabolising enzymes are polymorphic in man. The present review analyzes the importance of enzymes in the metabolism of anaesthetics and common polymorphisms related to the biotransformation of general anaesthetics and it raises hypotheses on genetic and non-genetics factors related to altered response to anaesthetics that require further investigation. Based on functional relevance and allele frequencies, we identify the most promising targets for the clinical use of pharmacogenomic techniques in anaesthesia to prevent altered pharmacokinetics or adverse drug effects.
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PMID:Polymorphic drug metabolism in anaesthesia. 1944 86

The contribution of the polymorphic markers of the CHRNA5/A3, CYP2A6, NQO1, XPC, XRCC1, XRCC3, XPD, XPA genes to chronic obstructive pulmonary disease has been assessed. For this purpose, analysis of the gene polymorphisms in case/control groups in Tatar population has been performed. The CHRNA5 (rs16969968) (P = 0.0001, OR = 2.24), CHRNA3 (rs1051730) (P = 0.0001, OR = 2.72) were associated with significantly high risk of chronic obstructive pulmonary disease in recessive model. The disease risk was higher in homozygous carriers of normal allele of CYP2A6 (del) (P = 0.00001, OR = 2.77). Analysis showed an association of the NQO1 (rs1131341), XRCC1 (rs25487), XRCC3 (rs861539), XPC (rs2228001) and XPA (rs1800975) (P = 0.000001, OR = 2.67; P = 0.00001, OR = 0.51; P = 0.0003, OR = 1.76; P = 0.0004, OR = 0.54 and P = 0.007, OR = 0.74) in additive model with chronic obstructive pulmonary disease. We found a significant gene-by-environment interaction of smoking status and XPA (rs1800975) (Pinteract = 0.002); rs16969968, rs1051730 of CHRNA3/5 genes were significantly associated with chronic obstructive pulmonary disease only in smokers. The relationship between the CYP2A6(CYP2A6*4) and smoking pack-years was found (P = 0.0019). The TT genotype of XRCC3 (rs861539) were associated with decreased of lung function parameters: vital capacity % (P = 0.0487), forced vital capacity (%) (P = 0.0032) and forced expiratory volume in 1 s (%) (P = 0.02). The relationship between the XPA (rs1800975) and forced expiratory volume in 1 s (%) (P = 0.0028) was found.
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PMID:[Association of the nicotine and cigarette smoke toxicants metabolic (CHRNA3/5, CYP2A6, NQO1) and DNA repair genes (XRCC1, XRCC3, XPC, XPA) with chronic obstructive pulmonary disease]. 2584 34

Tanshinone I (TSI) is a lipophilic diterpene in Salvia miltiorrhiza with versatile pharmacological activities. However, metabolic pathway of TSI in human is unknown. In this study, we determined major metabolites of TSI using a preparation of human liver microsomes (HLMs) by HPLC-UV and Q-Trap mass spectrometer. A total of 6 metabolites were detected, which indicated the presence of hydroxylation, reduction as well as glucuronidation. Selective chemical inhibition and purified cytochrome P450 (CYP450) isoform screening experiments revealed that CYP2A6 was primarily responsible for TSI Phase I metabolism. Part of generated hydroxylated TSI was glucuronidated via several glucuronosyltransferase (UGT) isoforms including UGT1A1, UGT1A3, UGT1A7, UGT1A9, as well as extrahepatic expressed isoforms UGT1A8 and UGT1A10. TSI could be reduced to a relatively unstable hydroquinone intermediate by NAD(P)H: quinone oxidoreductase 1 (NQO1), and then immediately conjugated with glucuronic acid by a panel of UGTs, especially UGT1A9, UGT1A1 and UGT1A8. Additionally, NQO1 could also reduce hydroxylated TSI to a hydroquinone intermediate, which was immediately glucuronidated by UGT1A1. The study demonstrated that hydroxylation, reduction as well as glucuronidation were the major pathways for TSI biotransformation, and six metabolites generated by CYPs, NQO1 and UGTs were found in HLMs and S9 subcellular fractions.
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PMID:Metabolic characteristics of Tanshinone I in human liver microsomes and S9 subcellular fractions. 2935 26