RGD Reference Report - Functional polymorphism of detoxification gene NQO1 predicts intensity of empirical treatment of childhood asthma. - Rat Genome Database

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

Authors: Goodrich, GG  Goodman, PH  Budhecha, SK  Pritsos, CA 
Citation: Goodrich GG, etal., Mutat Res. 2009 Mar 31;674(1-2):55-61. Epub 2008 Nov 5.
RGD ID: 5135006
Pubmed: PMID:19027876   (View Abstract at PubMed)
DOI: DOI:10.1016/j.mrgentox.2008.10.009   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
asthma  IDA 5135006DNA:SNP:exon:c. 609C>T (human)RGD 
asthma  ISONQO1 (Homo sapiens)5135006; 5135006DNA:SNP:exon:c. 609C>T (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Nqo1  (NAD(P)H quinone dehydrogenase 1)

Genes (Mus musculus)
Nqo1  (NAD(P)H dehydrogenase, quinone 1)

Genes (Homo sapiens)
NQO1  (NAD(P)H quinone dehydrogenase 1)


Additional Information