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Functional polymorphism of detoxification gene NQO1 predicts intensity of empirical treatment of childhood asthma.
Mutat Res. 2009 Mar 31; 674(1-2):55-61.MR

Abstract

The management of moderate to severe childhood asthma remains empirical. Genotypic variation has been proposed as a way to tailor specific pharmaceutical regimens to individual patients. The objective of this study was to determine the factors associated with asthma treatment progression, including functional polymorphisms of phase II detoxification enzymes, demographics, and environmental factors. In a study of 120 asthmatic children cared for in a single pediatric pulmonary practice, intensity of medical treatment over the year prior was modeled as a function of null mutations of glutathione S transferase (GST) M1 and T1, ile105val variant of GSTP1, and pro187ser variant of NAD(P)H:quinone oxidoreductase 1 (NQO1). The model included demographics, medical information, and environmental factors obtained via questionnaire analyzed with multivariate logistic regression and artificial neural networks. Multivariate logistic regression with bootstrapped validation identified a polymorphic variant of NQO1 as significantly contributing to increasing the odds of receiving more aggressive medical therapy (odds ratio, 11.56; p=0.0001). Parent income and education inversely correlated with medical treatment (odds ratio, 1.50; p=0.001 and odds ratio, 0.375; p=0.002, respectively). Age and reporting restricted physical activity due to asthma also impacted medical treatment (odds ratio, 0.63; p=0.0001 and odds ratio, 5.90; p=0.004, respectively). The optimism-adjusted discriminative ability (c-index) of the model was 0.881 (close to Bayes optimum of 0.902) with 80% overall classification accuracy. Our study supports the role of NQO1 polymorphism as an important factor determining the intensity of medical therapy in asthmatic children after adjusting for significance relating to parental income and education level, age, and restricted physical activity. Asthmatic children with a functional polymorphism of NQO1 may require more intensive pharmaceutical treatment to effectively control their asthma.

Authors+Show Affiliations

Environmental Sciences and Health, University of Nevada, Reno, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19027876

Citation

Goodrich, Geoffrey G., et al. "Functional Polymorphism of Detoxification Gene NQO1 Predicts Intensity of Empirical Treatment of Childhood Asthma." Mutation Research, vol. 674, no. 1-2, 2009, pp. 55-61.
Goodrich GG, Goodman PH, Budhecha SK, et al. Functional polymorphism of detoxification gene NQO1 predicts intensity of empirical treatment of childhood asthma. Mutat Res. 2009;674(1-2):55-61.
Goodrich, G. G., Goodman, P. H., Budhecha, S. K., & Pritsos, C. A. (2009). Functional polymorphism of detoxification gene NQO1 predicts intensity of empirical treatment of childhood asthma. Mutation Research, 674(1-2), 55-61. https://doi.org/10.1016/j.mrgentox.2008.10.009
Goodrich GG, et al. Functional Polymorphism of Detoxification Gene NQO1 Predicts Intensity of Empirical Treatment of Childhood Asthma. Mutat Res. 2009 Mar 31;674(1-2):55-61. PubMed PMID: 19027876.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Functional polymorphism of detoxification gene NQO1 predicts intensity of empirical treatment of childhood asthma. AU - Goodrich,Geoffrey G, AU - Goodman,Philip H, AU - Budhecha,Sonia K, AU - Pritsos,Chris A, Y1 - 2008/11/05/ PY - 2008/10/21/received PY - 2008/10/27/accepted PY - 2008/11/26/pubmed PY - 2009/6/6/medline PY - 2008/11/26/entrez SP - 55 EP - 61 JF - Mutation research JO - Mutat Res VL - 674 IS - 1-2 N2 - The management of moderate to severe childhood asthma remains empirical. Genotypic variation has been proposed as a way to tailor specific pharmaceutical regimens to individual patients. The objective of this study was to determine the factors associated with asthma treatment progression, including functional polymorphisms of phase II detoxification enzymes, demographics, and environmental factors. In a study of 120 asthmatic children cared for in a single pediatric pulmonary practice, intensity of medical treatment over the year prior was modeled as a function of null mutations of glutathione S transferase (GST) M1 and T1, ile105val variant of GSTP1, and pro187ser variant of NAD(P)H:quinone oxidoreductase 1 (NQO1). The model included demographics, medical information, and environmental factors obtained via questionnaire analyzed with multivariate logistic regression and artificial neural networks. Multivariate logistic regression with bootstrapped validation identified a polymorphic variant of NQO1 as significantly contributing to increasing the odds of receiving more aggressive medical therapy (odds ratio, 11.56; p=0.0001). Parent income and education inversely correlated with medical treatment (odds ratio, 1.50; p=0.001 and odds ratio, 0.375; p=0.002, respectively). Age and reporting restricted physical activity due to asthma also impacted medical treatment (odds ratio, 0.63; p=0.0001 and odds ratio, 5.90; p=0.004, respectively). The optimism-adjusted discriminative ability (c-index) of the model was 0.881 (close to Bayes optimum of 0.902) with 80% overall classification accuracy. Our study supports the role of NQO1 polymorphism as an important factor determining the intensity of medical therapy in asthmatic children after adjusting for significance relating to parental income and education level, age, and restricted physical activity. Asthmatic children with a functional polymorphism of NQO1 may require more intensive pharmaceutical treatment to effectively control their asthma. SN - 0027-5107 UR - https://www.unboundmedicine.com/medline/citation/19027876/Functional_polymorphism_of_detoxification_gene_NQO1_predicts_intensity_of_empirical_treatment_of_childhood_asthma_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1383-5718(08)00307-0 DB - PRIME DP - Unbound Medicine ER -