Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase and glutathione S-transferase M1 polymorphisms and childhood asthma.
Nicotinamide adenine dinucleotide (phosphate) reduced:quinone oxidoreductase (NQO1) and glutathione S-transferase (GST) M1 are phase II enzymes important in response to oxidative stress, such as occurs during exposure to ozone. We examined the relationship between functionally significant polymorphisms in NQO1 (Pro187Ser) and GSTM1 (homozygous deletion) and asthma risk in children with high lifetime exposure to ozone. We enrolled children with asthma from the allergy referral clinic at a public pediatric hospital in Mexico City, together with their parents. We assayed for the Pro187Ser polymorphism in NQO1 using a polymerase chain reaction-restriction fragment length polymorphism assay and for the presence of GSTM1 by polymerase chain reaction among 218 case-parent triads. We did not find strong evidence of an association between NQO1 genotype alone and asthma risk. However, among subjects with homozygous deletion of GSTM1, carriers of a serine allele were at significantly reduced risk of asthma compared with Pro/Pro homozygotes (relative risk = 0.4; 95% confidence interval, 0.2-0.8). The p value for difference in relative risk for NQO1 by GSTM1 genotype = 0.013. These data are consistent with a protective effect of the NQO1 Ser allele in this population of GSTM1-null children with high ozone exposure.
David
Gloria L
GL
National Institute of Environmental Health Sciences, PO Box 12233, MD D2-01, Research Triangle Park, NC 27709, USA. davidbe1@niehs.nih.gov
Romieu
Isabelle
I
Sienra-Monge
Juan Jose
JJ
Collins
William J
WJ
Ramirez-Aguilar
Matiana
M
del Rio-Navarro
Blanca Estela
BE
Reyes-Ruiz
Norma Isabel
NI
Morris
Richard W
RW
Marzec
Jacqueline M
JM
London
Stephanie J
SJ
D000293:Adolescent; D001249:Asthma / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics*; D008297:Male; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D009249:NADP / Q000235:genetics*; D010083:Oxidants, Photochemical / Q000009:adverse effects; D010126:Ozone / Q000009:adverse effects; D012150:Polymorphism, Restriction Fragment Length; D018570:Risk Assessment
D005982:Glutathione Transferase; D016660:NAD(P)H Dehydrogenase (Quinone); D009249:NADP; D010083:Oxidants, Photochemical; D010126:Ozone; C447479:NQO1 protein, human