Functional polymorphism of detoxification gene NQO1 predicts intensity of empirical treatment of childhood asthma

Goodrich, Geoffrey G.; Goodman, Philip H.; Budhecha, Sonia K.; Pritsos, Chris A.

doi:10.1016/j.mrgentox.2008.10.009

Cited by 7 publications

(9 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally we are able to tease out an apparent "extensive metabolizer" subset of individuals who we know cannot be polymorphic, which probably represents environmental plasticity in NQO1 in this population. Although the effects of NQO1 slow metabolizer polymorphisms/phenotypes have been extensively studied in the context of susceptibility to cancer and effects on drug metabolism, demonstrating environmental mechanisms for enzyme plasticity in human tissues is far more rare (David et al, 2003;Guha et al, 2008;Goodrich et al, 2009;Han et al, 2009;Martin et al, 2009;Vijayakrishnan and Houlston, 2010;Kolesar et al, 2011;Tsvetkov et al, 2011;Li and Zhou, 2014;Lin et al, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Associations between NQO1 polymorphisms, in particular the lowactivity C609T variant, and childhood diseases such as asthma and leukemia have been demonstrated (David et al, 2003;Guha et al, 2008;Goodrich et al, 2009;Vijayakrishnan and Houlston, 2010;Li and Zhou, 2014). In the adult population, increased cardiovascular and cancer risks (Han et al, 2009;Martin et al, 2009;Kolesar et al, 2011;Lin et al, 2014) as well as increasing severity of Alzheimer's disease in the elderly have also been linked to NQO1 polymorphisms (Tsvetkov et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

Rougée

Riches

Berman

et al. 2016

Drug Metabolism and Disposition

View full text Add to dashboard Cite

The NADPH dehydrogenase quinone oxido-reductase 1 (NQO1) enzyme is an antioxidant and metabolic enzyme that performs two electron reduction of quinones and other chemicals. Based on the physiologic role(s) of NQO1, we hypothesized that expression and activity of this enzyme would vary with age and other demographic variables. Cytosols from 117 archived human livers were investigated for changes in NQO1 with age, sex, obesity, and ethnicity. Protein expression but not activity of NQO1 was weakly negatively correlated with age (Spearman r = -0.2, P = 0.03). No sex differences were observed for either protein expression or activity and for ethnicity; Caucasians had greater NQO1 activity than Asians (P < 0.05). Overweight children had statistically significantly higher NQO1 activity as compared with ideal weight children (P < 0.05) although this difference was not observed in adults. These findings establish that NQO1 is approximately as active in children as adults. However, modeled NQO1 clearance (both allometric and physiologically based pharmacokinetics) predicted maturation at 23 to 26 years. This is almost certainly an overestimate, with error in the model resulting from a small sample size and inability to scale for age-related changes in hepatic cellularity and/or cytosolic protein content, and indicates a delay in reaching maximum clearance through the NQO1 pathway that is affected by physiologic development as much, or more than, biochemical development. Obesity may increase hepatic NQO1 activity in children, which is likely a protective mechanism in oxidative stress, but may also have significant implications for drug and chemical disposition in obese children.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

Rougée

Riches

Berman

et al. 2016

Drug Metabolism and Disposition

View full text Add to dashboard Cite

show abstract

“…Functional polymorphism of NQO1 gene with conjugation of GSTM1 null variant can have a protective effect in relation to asthma risk (David et al, 2003). For individuals already exhibiting disease status, a decrease or loss of NQO1 activity due to mutation, can play a role by increasing the risk of severity (Goodrich et al, 2009). Polymorphism in NQO1 gene may be an important factor determining the intensity of medical therapy in asthmatic children.…”

Section: Genetic Changes In Bronchial Asthma Related To Oxidative Damagementioning

confidence: 99%

“…Polymorphism in NQO1 gene may be an important factor determining the intensity of medical therapy in asthmatic children. Asthmatic children with functional polymorphism of NQO1 may require more intensive pharmaceutical treatment to effectively control their asthma (Goodrich et al, 2009). …”

Section: Genetic Changes In Bronchial Asthma Related To Oxidative Damagementioning

confidence: 99%

Oxidative Damage and Bronchial Asthma

Babušíková¹,

Jurečeková²,

Evinová³

et al. 2012

Respiratory Diseases

View full text Add to dashboard Cite

“…Phase II detoxification enzymes, particularly classes of GSTs, play an important role in inflammatory responses triggered by xenobiotic or reactive oxygen compounds [4]. The GSTM1 and GSTT1 are two important phase II enzymes that protect the airways from oxidative stress [5].…”

Section: Introductionmentioning

confidence: 99%

Glutathione S transferase theta1 and mu1 gene polymorphisms and phenotypic expression of asthma in Egyptian children: a case–control study

et al. 2014

View full text Add to dashboard Cite

BackgroundAsthma is the result of a complex interaction between environmental factors and genetic variants that confer susceptibility. The glutathione S-transferases (GSTT1 and GSTM1) are phase II enzymes thought to protect the airways from oxidative stress. Few and contradictory data are available on the association between asthma development and GSTT1 and GSTM1 polymorphisms in different ethnic groups. The current study aimed to investigate whether these polymorphisms are associated with asthma development in the Egyptian population.MethodsThe cross-sectional study was performed on 94 asthmatic children 6 -12 yrs and 90 matched healthy controls. Candidates were subjected to clinical evaluation and measurement of absolute blood eosinophilic count, total serum IgE, and GSTT1 and GSTM1 genotype by multiplex PCR technique.ResultsThe results for GSTT1 null genotype were 87.2% and 97.2% for asthmatic children and controls respectively and showed to be significantly more in controls (P =0.007, OR:0.683, CI: 0.034 -0.715). The results for GSTM1 null genotype were 50% and 61.1% for asthmatic children and controls respectively and showed to be nonsignificant (p = 0.130, OR: 1.000, CI: 0.54- 1.86). Also, no association was detected between GSTT1 and GSTM1 polymorphisms and atopic conditions or asthma severity.ConclusionThe significant detection of GSTT1 null genotype more in controls than in asthmatics with no association with other atopic manifestations or asthma severity and the lack of association detected between GSTM1 polymorphism in relation to asthma, atopy or asthma severity confirm the uncertain role of those genes in the development of asthma.

show abstract

Functional polymorphism of detoxification gene NQO1 predicts intensity of empirical treatment of childhood asthma

Cited by 7 publications

References 30 publications

The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

The Ontogeny and Population Variability of Human Hepatic NADPH Dehydrogenase Quinone Oxido-Reductase 1 (NQO1)

Oxidative Damage and Bronchial Asthma

Glutathione S transferase theta1 and mu1 gene polymorphisms and phenotypic expression of asthma in Egyptian children: a case–control study

Contact Info

Product

Resources

About