Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:1.6.5.2 (NQO1)
6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There is increasing evidence from epidemiological studies that genetic susceptibilities may modify the teratogenic effects of toxic chemicals. However, in contrast to tobacco smoke, few epidemiological studies have addressed environmental chemicals, such as polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans and polychlorinated biphenyls in regard to genetic susceptibility. Recent studies, including the Hokkaido Study of Environments and Children's Health, have investigated the impacts of both environmental and genetic factors on children's development. Several xenobiotic-metabolizing genes have been reported to confer genetic susceptibility to low birth weight. These genes seem to be influenced functionally by maternal smoking during pregnancy, itself a significant risk factor. In our study, we found that birth weight was significantly lower among infants born to smoking women having the specific AHR, CYP1A1, GSTM1, CYP2E1 and NQO1 genotypes. When combinations of these genotypes were considered, birth weight was even lower. On the other hand, congenital anomalies such as hypospadias seemed to be caused by environmental factors in conjunction with genetic predisposition as suggested by linkage in several case-control studies reported to low birth weight. We have found an association between maternal CYP1A1 genotype or low birth weight and the risk of hypospadias irrespective of smoking. At the same time, birth weight was negatively correlated with maternal blood concentrations of polychlorinated dibenzofurans. Further studies should elucidate the impact of genetic factors on adverse effects of exposures to dioxin-related chemicals.
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PMID:Exploiting gene-environment interaction to detect adverse health effects of environmental chemicals on the next generation. 1822 74

In order to examine whether a notification of genotypes related to a susceptibility to smoking has any influence on an intention to quit, a pilot study was conducted for 61 smokers out of 66 municipal government employees who attended an anti-smoking seminar in November 2005 or January 2006 (MG), and for 46 smokers (employees and students) on a medical campus (Tsurumai Campus) of Nagoya University (TC), who voluntarily responded to the study enrollment notice in August 2006. They were genotyped for four polymorphisms; GSTM1 null/present, GSTT1 null/present, NQO1 C609T, and CYP1A1 Ile/Val. For the MG group, their smoking habits were ascertained three times; at enrollment, one month later just before the genotype notification by in-house mail, and three months after the notification. The smoking cessation rate was 8.2%. For the TC group, their genotypes were mailed two weeks after blood sampling. The follow-up questionnaire three months after the genotype notification found a 10.9% cessation rate. Their stage of smoking cessation significantly improved after the genotype notification. This study demonstrated that the effects of the genotype notification in this context of smoking cessation were moderate and less remarkable than might have been expected. Although the genotype notification in TC improved their stage of readiness to quit smoking, additional skills or tools in support of the notification are needed to achieve a higher cessation rate.
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PMID:Smoking cessation after genotype notification: pilot studies of smokers employed by a municipal government and those on Nagoya University medical campus. 1835 Dec 34

In the present paper, we examined the incidence of polymorphic genes involved with the detoxification of exogenous chemicals, including carcinogens, namely GSTT1 (glutathione transferase theta1), GSTM1 (glutathione transferase micro1) and NQO1 (NAD(P)H:quinone oxidoreductase 1) in 60 Filipino paediatric patients with ALL (acute lymphoblastic leukaemia). We found a significantly high incidence of the GSTM1 null genotype in ALL children (71.7%) compared with 51.7% in the control group of children (P<0.05). The GSTT1 null genotype was observed in 35.0% and 33.3% of the ALL cases and the control subjects respectively, with no significant difference. Screening for NQO1 (609C>T) mutant alleles showed a high incidence of the NQO1 C/C genotype (NQO1 homozygous wild-type allele genotype) in 60.0% of ALL cases and was significantly higher than in the control group (23.3%) (P<0.01). These GSTM1 null and NQO1 wild-type genotypes are independently associated with the risk of ALL in Filipino patients. When these two genotypes, GSTM1 null and NQO1 C/C, were combined, the hazard rate for childhood leukaemia was significantly increased (P<0.001). We also noticed that the incidences of GSTM1 null mutations and the NQO1 C/C genotype were significantly higher among Filipinos. These findings suggest a possible role of the GSTM1 null and NQO1 C/C genotypes in the susceptibility of paediatric ALL cases in the Philippines.
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PMID:Prevalence of GSTT1, GSTM1 and NQO1 (609C>T) in Filipino children with ALL (acute lymphoblastic leukaemia). 1844 11

There is large variation between individuals in their response to air pollutants. This review summarises the existing evidence that genetic factors influence the mechanisms of lung injury caused by air pollutants. Genetic association studies have compared the adverse effects of air pollutants between subjects with specific genotypes in biologically relevant genes. In human studies of ozone exposure, polymorphisms in oxidative stress genes (NQO1, GSTM1, GSTP1) modify respiratory symptoms, lung function, biomarkers and risk of asthma. Inflammatory gene polymorphisms (TNF) influence the lung function response to ozone, and the effect of different levels of ozone on the development of asthma. Polymorphisms in oxidative stress genes (GSTM1, GSTP1) alter the response to combined exposure to ragweed pollen and diesel exhaust particles. Importantly, polymorphisms in an oxidative stress gene (GSTM1) have predicted patients with asthma who benefit from antioxidant supplementation in Mexico City, which has chronically high ozone exposure. Genetic linkage studies of families have not been feasible for studying the effects of air pollution in humans, but some progress has been made with pedigrees of specially bred mice, in identifying chromosomal regions linked to effects of ozone or particles. A high priority now, in addition to avoiding exposure in the most susceptible people, is to clearly identify the most effective and safe chemopreventive agents for individuals who are genetically susceptible to the adverse effects of air pollution (eg, antioxidants to be taken during high ozone levels).
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PMID:Genetic susceptibility to the respiratory effects of air pollution. 1963 9

Tobacco smoking, alcohol drinking, and occupational exposures to polycyclic aromatic hydrocarbons are the major proven risk factors for human head and neck squamous-cell cancer (HNSCC). Major research focus on gene-environment interactions concerning HNSCC has been on genes encoding enzymes of metabolism for tobacco smoke constituents and repair enzymes. To investigate the role of genetically determined individual predispositions in enzymes of xenobiotic metabolism and in repair enzymes under the exogenous risk factor tobacco smoke in the carcinogenesis of HNSCC, we conducted a case-control study on 312 cases and 300 noncancer controls. We focused on the impact of 22 sequence variations in CYP1A1, CYP1B1, CYP2E1, ERCC2/XPD, GSTM1, GSTP1, GSTT1, NAT2, NQO1, and XRCC1. To assess relevant main and interactive effects of polymorphic genes on the susceptibility to HNSCC we used statistical models such as logic regression and a Bayesian version of logic regression. In subgroup analysis of nonsmokers, main effects in ERCC2 (Lys751Gln) C/C genotype and combined ERCC2 (Arg156Arg) C/A and A/A genotypes were predominant. When stratifying for smokers, the data revealed main effects on combined CYP1B1 (Leu432Val) C/G and G/G genotypes, followed by CYP1B1 (Leu432Val) G/G genotype and CYP2E1 (-70G>T) G/T genotype. When fitting logistic regression models including relevant main effects and interactions in smokers, we found relevant associations of CYP1B1 (Leu432Val) C/G genotype and CYP2E1 (-70G>T) G/T genotype (OR, 10.84; 95% CI, 1.64-71.53) as well as CYP1B1 (Leu432Val) G/G genotype and GSTM1 null/null genotype (OR, 11.79; 95% CI, 2.18-63.77) with HNSCC. The findings underline the relevance of genotypes of polymorphic CYP1B1 combined with exposures to tobacco smoke.
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PMID:Head and neck squamous-cell cancer and its association with polymorphic enzymes of xenobiotic metabolism and repair. 1856 91

Aromatic amines (AAs) and polycyclic aromatic hydrocarbons (PAHs) are carcinogens present in tobacco smoke and functional polymorphisms in NAT2 and GSTM1 metabolizing genes are associated with increased bladder cancer risk. We evaluated whether genetic variation in other candidate metabolizing genes are also associated with risk. Candidates included genes that control the transcription of metabolizing genes [aryl hydrocarbon receptor (AHR), AHRR and aryl hydrocarbon nuclear translocator (ARNT)] and genes that activate/detoxify AA or PAH (AKR1C3, CYP1A1, CYP1A2, CYP1B1, CYP3A4, EPHX1, EPHX2, NQO1, MPO, UGT1A4, SULT1A1 and SULT1A2). Using genotype data from 1150 cases of urothelial carcinomas and 1149 controls from the Spanish Bladder Cancer Study, we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. Based on a test for trend, we observed 10 non-redundant single-nucleotide polymorphisms (SNPs) in five genes (AKR1C3, ARNT, CYP1A1, CYP1B1 and SULT1A2) significantly associated with bladder cancer risk. We observed an inverse association with risk for the AKR1C3 promoter SNP rs1937845 [OR (95% CI) for heterozygote and homozygote variant compared with common homozygote genotype were 0.86 (0.70-1.06) and 0.74 (0.57-0.96), respectively; P for trend = 0.02]. Interestingly, genetic variation in this region has been associated with lung, non-Hodgkin lymphoma and prostate cancer risk. Analysis of additional SNPs to capture most (approximately 90%) of common genetic variation in AKR1C3 and haplotype walking analyses based on all AKR1C3 SNPs (n = 25) suggest two separate regions associated with bladder cancer risk. These results indicate that genetic variation in carcinogen-metabolizing genes, particularly AKR1C3, could be associated with bladder cancer risk.
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PMID:Bladder cancer risk and genetic variation in AKR1C3 and other metabolizing genes. 1863 53

The genetic background may modify the individual's risk of developing cancer. We performed a case-control study to test the impact of genomic polymorphisms of 9 genes involved in xenobiotics detoxification and DNA repair in myelodysplastic syndromes (MDS). Frequencies of polymorphic variants of RAD51, XRCC3, NQO1, GSTA1, GSTM1, GSTT1, CYP3A4 and XPD enzymes were similar in patients and controls. On the other hand, the GSTP1-105Val allele was associated to an increased risk of MDS (O.R. 1.66; p=0.04) and to higher probability of overall survival in the low/intermediate-1 IPSS risk group (p=0.008). The GSTP1-Ile105Val polymorphism is likely to influence MDS risk and prognosis.
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PMID:Polymorphisms of detoxification and DNA repair enzymes in myelodyplastic syndromes. 1902 52

To explore the potential role for estrogen in lung cancer susceptibility, candidate single-nucleotide polymorphism (SNPs) in tobacco and estrogen metabolism genes were evaluated. Population-based cases (n = 504) included women aged 18-74, diagnosed with NSCLC in metropolitan Detroit between November 2001 and October 2005. Population-based controls (n = 527) were identified through random digit dialing and matched on race and age. Eleven SNPs in 10 different genes were examined in relation to risk: CYP1A1 Msp1, CYP1A1 Ile462Val, CYP1B1 Leu432Val, CYP17, CYP19A1, XRCC1 Gln399Arg, COMT Val158Met, NQO1 Pro187Ser, GSTM1, GSTT1 and GSTP1 Ile105Val. Lung cancer risk associated with individual SNPs was seen for GSTP1 [A allele; odds ratio (OR) = 1.85; 95% confidence interval (CI), 1.04-3.27] and XRCC1 (A/A genotype; OR = 1.68; 95% CI, 1.01-2.79) in white women and CYP1B1 (G allele; OR = 11.1; 95% CI, 1.18-104) in black women smokers. White women smokers carrying two risk genotypes at the following loci were at increased risk of lung cancer compared with individuals not carrying risk alleles at these loci: CYP17 and GSTM1, COMT and GSTM1, CYP17 and GSTT1, XRCC1 and GSTP1, CYP1B1 and XRCC1 and COMT and XRCC1. The most parsimonious model of lung cancer risk in white smoking women included age, family history of lung cancer, history of chronic lung disease, pack-years, body mass index, XRCC1 A/A genotype, GSTM1 null and COMT A/G or G/G genotype. These findings support the need for continued study of estrogen in relation to lung cancer risk. Polymorphisms in the tobacco metabolism, estrogen metabolism and DNA repair pathways will be useful in developing more predictive models of individual risk.
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PMID:Tobacco and estrogen metabolic polymorphisms and risk of non-small cell lung cancer in women. 1917 90

3H-1,2-dithiole-3-thione (D3T), a cruciferous organosulfur compound, induces cytoprotective enzymes in animal cardiovascular cells. However, it remains unknown if D3T also upregulates antioxidants and phase 2 enzymes in human cardiomyocytes, and protects against cell injury induced by oxidative/electrophilic species as well as doxorubicin. In this study, we found that D3T (10-50 muM) potently induced a series of antioxidants and phase 2 enzymes in primary cultured human cardiomyocytes, including superoxide dismutase (SOD), glutathione (GSH), glutathione reductase (GR), glutathione peroxidase (GPx) glutathione S-transferase (GST), NAD(P)H:quinone oxidoreductase 1 (NQO1), aldose reductase (AR), and heme oxygenase (HO). D3T treatment also caused elevation of SOD, GSH, GR, GPx and GST in the isolated mitochondria. We also observed a time-dependent induction by D3T of mRNA expression for Cu,ZnSOD, MnSOD, gamma-glutamylcysteine ligase, GR, GSTA1, GSTM1, NQO1, AR, and HO-1. Pretreatment with D3T conferred concentration-dependent protection against cell injury induced by xanthine oxidase (XO)/xanthine, H(2)O(2), 3-morpholinosydnonimine, 4-hydroxy-2-nonenal, and doxorubicin. Pretreatment with D3T also reduced the formation of intracellular reactive oxygen species by XO/xanthine, H(2)O(2), and doxorubicin. In conclusion, this study demonstrated that D3T potently upregulated many antioxidants and phase 2 enzymes in human cardiomyocytes, which was accompanied by increased resistance to oxidative/electrophilic stress and doxorubicin toxicity.
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PMID:Cruciferous dithiolethione-mediated coordinated induction of total cellular and mitochondrial antioxidants and phase 2 enzymes in human primary cardiomyocytes: cytoprotection against oxidative/electrophilic stress and doxorubicin toxicity. 1917 75

Environmental tobacco smoke (ETS) exposure might increase the risk for childhood asthma, and we hypothesized the effect may be modified by the phase II genes NAD(P)H: quinone oxidoreductase 1 (NQO1) and glutathione S-transferase (GST) M1. To investigate the genetic and environmental associations with asthma, GSTM1 and NQO1 functional polymorphisms and ETS were analyzed in a two-staged cross-sectional study among elementary schoolchildren in Taiwan. Multiple logistic regression analysis revealed a significant association between the Ser allele of the NQO1 Pro187Ser polymorphism and asthma (OR=1.6, 95% CI 1.3-1.8). Although GSTM1 genotype itself was not significantly associated with asthma (OR=1.0, 95% CI 0.8-1.1), the GSTM1 genotype modified the association between the NQO1 polymorphism and asthma in children exposed to ETS (p=0.0002). The NQO1 gene might be involved in the development of asthma, especially in children carrying the GSTM1 null genotype who are exposed to ETS.
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PMID:NAD(P)H: Quinone oxidoreductase 1, glutathione S-transferase M1, environmental tobacco smoke exposure, and childhood asthma. 1959 59


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