Importantly, polymorphisms in an oxidative stress gene (GSTM1) have predicted patients with asthma who benefit from antioxidant supplementation in Mexico City, which has chronically high ozone exposure.
The GSTM1 null genotype was found to be protective from the development of asthma in atopic subjects (odds ratios 0.55, 95% confidence interval 0.34-0.90; P=0.017).
To investigate the association of TNF G-308A with asthma and wheezing and to determine whether these associations vary with ozone exposure and GSTM1 and GSTP1 genotype.
The current authors investigated the relationships between common polymorphisms in two genes involved in response to oxidative stress, i.e. glutathione S-transferases M1 (GSTM1) and P1 (GSTP1), and both respiratory symptoms and lung function in response to ozone among childhood asthmatics.
Genetic polymorphisms of the GSTM1 and GSTT1 genes, both individually and in combination, were not associated with the development of allergic diseases including asthma in the Czech population, the GSTM1 gene variability, however, may influence lung functions in our asthmatics.
Three- to 12-year-olds who are null for GSTM1 or homozygous for the GSTP1Val105 allele are more susceptible to asthma associated with environmental tobacco smoke exposure than those with more intact glutathione S-transferase status.
In children lacking the GSTM1 allele who were exposed to current ETS the risk for current asthma (OR 5.5, 95% CI 1.6 to 18.6) and asthma symptoms such as wheeze ever (OR 2.8, 95% CI 1.3 to 6.0), current wheezing (OR 4.7, 95% CI 1.8 to 12.6) and shortness of breath (OR 8.9, 95% CI 2.1 to 38.4) was higher than in GSTM1 positive individuals without ETS exposure.
We found that asthmatic patients with two copies of GSTM1 were significantly underrepresented (p<0.0005) and the significance increased by 10-fold when only atopic asthmatics were analyzed (p<0.00005).
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).
Statistically significant increases in asthma risk were also observed among the whole study population for the concurrent presence of the GSTM1 null genotype and either NAT1 (odds ratio [OR] 4.53, 95% CI 1.76 to 11.6) or NAT2 (OR 3.12, 95% CI 1.11 to 8.78) slow acetylator genotypes, and of NAT1 and NAT2 slow acetylator genotypes (OR 4.20, 95% CI 1.51 to 11.6).
The rapid acetylator, GSTM1 null and GSTT1 null genotypes with a medical history of asthma or tuberculosis combinations were significant risk factors in Korean subjects.