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)

Metabolic enzymes involved in benzene activation or detoxification, including NAD(P)H, quinone oxidoreductase 1 (NQO1), cytochrome P450 2E1 (CYP2E1), myeloperoxidase (MPO), glutathione-S-transferase mu-1 (GSTM1), and glutathione-S-transferase theta-1 (GSTT1), were studied for their roles in human susceptibility to benzene poisoning. The potential interactions of these metabolic enzymes with lifestyle factors such as cigarette smoking and alcohol consumption were also explored. We studied 156 benzene-poisoning patients and 152 workers occupationally exposed to benzene in South China. Sequencing, denaturing HPLC, restriction fragment-length polymorphism, and polymerase chain reaction were used to detect polymorphisms on the promoters and complete coding regions of NQO1, CYP2E1, MPO, and the null genotypes of GSTM1 and GSTT1. Seventeen single nucleotide polymorphisms (SNPs) were identified in NQO1, CYP2E1, and MPO genes, including 6 novel SNPs in CYP2E1 and MPO. Of the subjects who smoked and drank alcohol, an 8.15-fold [95% confidence interval (CI), 1.43-46.50] and a 21.50-fold (95% CI, 2.79-165.79) increased risk of benzene poisoning, respectively, were observed among the subjects with two copies of NQO1 with a C-to-T substitution in cDNA at nucleotide 609 (c.609 C>T variation; i.e., NQO1 c.609 T/T) compared to those with the heterozygous or wild (NQO1 c.609 C/T and c.609 C/C) genotypes. Our data also indicated that individuals with CYP2E1 c.-1293 C/C and c.-1293 G/C, and NQO1 c.609 T/T, and GSTT1 null genotypes tended to be more susceptible to benzene toxicity. Our results suggest that the combined effect of polymorphisms in NQO1, CYP2E1, and GSTT1 genes and lifestyle factors might contribute to benzene poisoning.
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PMID:Association of genetic polymorphisms in CYP2E1, MPO, NQO1, GSTM1, and GSTT1 genes with benzene poisoning. 1246 Aug

Workers with chronic benzene poisoning (CBP) sometimes have a white blood cell count (WBC) below 4 x 10(9)/L even after cessation of workplace exposure to benzene for years. In order to explore this phenomenon, 120 workers with CBP were divided into two groups depending on the WBC, the mean diagnostic age of CBP, benzene exposure duration, and body mass index (BMI). The proportion of genotypes of cytochrome P450 2E1 (CYP2E1), glutathione-S-transferase mu-1 (GSTM1), glutathione-S-transferase theta-1 (GSTT1), myeloperoxidase (MPO), and NAD(P)H, quinone oxidoreductase 1 (NQO1) were compared between workers with WBC <4 x 10(9)/L and those with WBC > or =4 x 10(9)/L. With methods of logistic regression, a risk model was set up to predict the prognosis of CBP workers. The results indicated that the BMI of workers with WBC <4 x 10(9)/L was lower than that of workers with WBC of > or =4 x 10(9)/L (21.40 +/- 2.76 versus 23.09 +/- 3.36, P = 0.01), and the logistic regression model suggested there was a 4.5-fold increased risk among workers carrying GSTT1 null genotype (95% CI= 1.13- 17.54) compared with workers with GSTT1 non-null genotype. Our findings suggest that benzene exposure duration, BMI, and GSTT1 genotype may impact prognosis of the CBP workers.
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PMID:Genetic polymorphism of toxicant-metabolizing enzymes and prognosis of Chinese workers with chronic benzene poisoning. 1711 98