Association of glutathione-S-transferase omega haplotypes with susceptibility to chronic obstructive pulmonary disease.
Cigarette smoking is the main risk factor for developing the inflammatory lung disease chronic obstructive pulmonary disease (COPD). Differences in susceptibility among smokers have been attributed to a genetic predisposition. A recent publication on the Framingham Heart Study found a strong association of the Asn142Asp SNP in Glutatthione-S-transferase Omega (GSTO) 2 with forced expiratory volume in the first second (FEV(1)) and forced vital capacity (FVC). FEV(1) is the main parameter reflecting the degree of airflow limitation in patients with COPD. Therefore the present study was undertaken to investigate whether the Asn142Asp polymorphism in GSTO2 occurs more frequently in patients with COPD than healthy subjects and to replicate the finding that it strongly correlates with FEV(1). Furthermore, the Ala140Asp substitution in GSTO1 was examined. Genotyping was carried out in 195 healthy controls and 355 patients with COPD. The results demonstrate that the Asn142Asp polymorphism in GSTO2 and the GSTO1140Asp/GSTO2142Asp haplotype were associated with increased risk of COPD. However, single-marker and haplotype-based analyses failed to reveal an association between lung function parameters and investigated non-synonymous coding SNPs in the GSTO genes. In conclusion, GSTO2 is a candidate gene for COPD, but is not associated with FEV(1).
Yanbaeva
Dilyara G
DG
Department of Respiratory Medicine, Nutrition and Toxicology Research Institute Maastricht, Maastricht University Medical Centre, Maastricht, The Netherlands.
Wouters
Emiel F M
EF
Dentener
Mieke A
MA
Spruit
Martijn A
MA
Reynaert
Niki L
NL
D000368:Aged; D016022:Case-Control Studies; D005260:Female; D005541:Forced Expiratory Volume / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009426:Netherlands; D017354:Point Mutation; D020641:Polymorphism, Single Nucleotide; D029424:Pulmonary Disease, Chronic Obstructive / Q000453:epidemiology / Q000209:etiology / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects; D014797:Vital Capacity / Q000235:genetics
C490476:GSTO1 protein, human; C492569:GSTO2 protein, human; D005982:Glutathione Transferase