Oxidative stress and genetic and epidemiologic determinants of oxidant injury in childhood asthma.
BACKGROUND
The factors contributing to the oxidant/antioxidant imbalance in asthma are incompletely understood.


OBJECTIVE
To determine the factors associated with oxidative stress including asthma severity and the genotype of the antioxidant enzymes.


METHODS
A total of 196 children with mild asthma, 116 children with moderate-severe asthma, and 2 healthy control groups (187 and 68 children) were included in the study. Plasma levels of malondialdehyde were measured as the indicator of oxidative stress, and reduced glutathione levels as the indicator of antioxidant defense. Children were genotyped for null variants of glutathione S transferase (GST) T1 and GSTM1, and ile105val variant of GSTP1. Risk factors were analyzed with multivariate logistic regression.


RESULTS
Systemic levels of malondialdehyde increased and reduced glutathione levels decreased significantly from healthy controls to patients with mild asthma and then to patients with moderate-severe asthma (P < .001 for each). Multivariate logistic regression identified asthma and asthma severity as independent factors associated with oxidative stress (odds ratio between 17 and 56; P < .001). Children with asthma with GSTP1 val/val genotype had higher malondialdehyde and lower glutathione levels compared with other genotypes (P = .023 and P = .014, respectively). GSTP1 val/val genotype was independently associated with asthma severity (odds ratio, 4.210; 95% CI, 1.581-11.214; P = .004).


CONCLUSIONS
Our study indicates the presence of a strong oxidative stress in children with asthma that increases with the severity of the disease. In this population, val/val genotype at GSTP1 ile105val locus may be an important factor in determining the degree of oxidant injury.


CONCLUSIONS
Children with asthma with val/val genotype at GSTP1 ile105val locus may be good candidates for supplemental antioxidant therapy.
Ercan
Hulya
H
Pediatric Allergy and Asthma Unit, School of Medicine, Pediatric Allergy and Asthma Unit, Hacettepe, Ankara, Turkey.
Birben
Esra
E
Dizdar
Evrim A
EA
Keskin
Ozlem
O
Karaaslan
Cagatay
C
Soyer
Ozge U
OU
Dut
Raziye
R
Sackesen
Cansin
C
Besler
Tanju
T
Kalayci
Omer
O
D000293:Adolescent; D001249:Asthma / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D005260:Female; D005838:Genotype; D005978:Glutathione / Q000378:metabolism; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D016877:Oxidants / Q000009:adverse effects*; D018384:Oxidative Stress / Q000235:genetics / Q000276:immunology*; D012720:Severity of Illness Index
D016877:Oxidants; D008315:Malondialdehyde; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D005978:Glutathione