title: Glutathione-S-transferase M1, M3, P1 and T1 polymorphisms and severity of lung disease in children with cystic fibrosis.
abstract: OBJECTIVE
  Progression and severity of lung disease differs markedly and early between patients with cystic fibrosis (CF). We investigated the hypothesis that polymorphisms in the detoxifying enzymes glutathione-S-transferase (GST) could influence phenotypic presentation of lung disease in CF.
  
  
  METHODS
  Genotypes for GSTM1, GSTM3, GSTP1 and GSTT1 were determined in a cohort of 146 children with CF by PCR-based methods. Pulmonary function, assessed by spirometric measures of forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), was analysed in children at the age of 9.
  
  
  RESULTS
  No association between spirometric measurements, and GSTM1, GSTP1 or GSTT1 genotypes was found. As compared with patients homozygous for GSTM3*A allele, CF children carrying the GSTM3*B allele displayed a significant better lung function, assessed by both mean values of FEV1 and of FVC (respectively P = 0.01 and P = 0.002). These correlations remained significant after adjustment for potential confounding factors (respectively adjusted P = 0.008 and P = 0.002) and also in subgroups of CF patients who carry the deltaF508 CFTR mutation. Haplotype analysis of GSTM3 in combination with GSTM1 indicated that the positive impact of GSTM3*B allele on pulmonary performances was barely influenced by the GSTM1 genotypes of CF children.
  
  
  CONCLUSIONS
  These data provide the first evidence suggesting that polymorphism of the GSTM3 gene contributes to clinical severity in CF, which may have prognostic significance and could prompt to start a more targeted therapy in young patients with CF.
authors.affiliation: INSERM E213 and Department of Pediatrics, Trousseau Children's Hospital, Paris, France.
authors.forename: Cyril
authors.initials: C
authors.lastname: Flamant
authors.forename: Alexandra
authors.initials: A
authors.lastname: Henrion-Caude
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Boëlle
authors.forename: François
authors.initials: F
authors.lastname: Brémont
authors.forename: Jacques
authors.initials: J
authors.lastname: Brouard
authors.forename: Bertrand
authors.initials: B
authors.lastname: Delaisi
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Duhamel
authors.forename: Christophe
authors.initials: C
authors.lastname: Marguet
authors.forename: Michel
authors.initials: M
authors.lastname: Roussey
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Miesch
authors.forename: Michèle
authors.initials: M
authors.lastname: Boulé
authors.forename: Richard C
authors.initials: RC
authors.lastname: Strange
authors.forename: Annick
authors.initials: A
authors.lastname: Clement
mesh_terms: D000293:Adolescent; D000328:Adult; D001483:Base Sequence; D002648:Child; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000235:genetics* / Q000503:physiopathology; D017931:DNA Primers; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D008875:Middle Aged
chemical_list: D017931:DNA Primers; D007527:Isoenzymes; D005982:Glutathione Transferase