title: Glutathione-S-transferase gene polymorphisms (GSTT1, GSTM1, GSTP1) as increased risk factors for asthma.
abstract: OBJECTIVE
  Asthma is a complex multifactorial disease with an obvious genetic predisposition, immunological aberration, and involvement of noxious environmental factors. Polymorphisms of the glutathione-S-transferase (GST) genes are known risk factors for some environmentally-related diseases. In the present study, the hypothesis that polymorphisms in the GSTT1, GSTM1 and GSTP1 genes are associated with atopic and nonatopic asthma was examined.
  
  
  METHODS
  The study population consisted of 103 unrelated healthy individuals and 101 patients with bronchial asthma (64 atopic, 37 nonatopic). Asthma was diagnosed according to the American Thoracic Society statement. Genotyping of polymorphisms in the GSTT1, GSTM1 and GSTP1 genes was performed using real time polymerase chain reaction with a Light Cycler instrument and hybridization probes in combination with the Light Cycler DNA master hybridization probes kit.
  
  
  RESULTS
  Patients with atopic asthma (34.4%) had a higher prevalence of the GSTT1 null genotype than the nonatopic asthma patients (13.5%; OR = 3.83; 95% CI, 1.24-11.78). Asthma patients (63.4%) had a higher prevalence of the GSTM1 null genotype than the control group (40.8%; OR = 2.34; 95% CI, 1.31-4.20). Subjects with the GSTP1 homozygous Val/Val genotype had a 3.55-fold increased risk of having atopic asthma compared to nonatopic asthma (OR = 3.55; 95% CI, 1.10-12.56).
  
  
  CONCLUSIONS
  These results suggest that the GSTT1 and GSTM1 null genotypes and the GSTP1 Val/Val polymorphism may play important roles in asthma pathogenesis. It is possible that intermediate electrophilic metabolites, arising in the first phase of detoxification, are not metabolized by GST enzymes in asthmatic patients and are not excreted. These intermediate metabolites may damage cells and generate oxidative stress, and so contribute to the pathogenesis of asthma.
authors.affiliation: Deparment of Biochemistry, Medical Faculty, Mersin University, Mersin, Turkey. lutamer@yahoo.com
authors.forename: Lülüfer
authors.initials: L
authors.lastname: Tamer
authors.forename: Mukadder
authors.initials: M
authors.lastname: Calikoğlu
authors.forename: Nurcan Aras
authors.initials: NA
authors.lastname: Ates
authors.forename: Hatice
authors.initials: H
authors.lastname: Yildirim
authors.forename: Bahadir
authors.initials: B
authors.lastname: Ercan
authors.forename: Emel
authors.initials: E
authors.lastname: Saritas
authors.forename: Ali
authors.initials: A
authors.lastname: Unlü
authors.forename: Ugur
authors.initials: U
authors.lastname: Atik
mesh_terms: D001249:Asthma / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D005828:Genetics, Population; D005838:Genotype; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D012307:Risk Factors; D014421:Turkey / Q000453:epidemiology
chemical_list: D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; D007527:Isoenzymes; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human