title: Genetic interaction of GSH metabolic pathway genes in cystic fibrosis.
abstract: BACKGROUND
  Cystic fibrosis (CF) is a monogenic disease caused by CFTR gene mutations, with clinical expression similar to complex disease, influenced by genetic and environmental factors. Among the possible modifier genes, those associated to metabolic pathways of glutathione (GSH) have been considered as potential modulators of CF clinical severity. In this way it is of pivotal importance investigate gene polymorphisms at Glutamate-Cysteine Ligase, Catalytic Subunit (GCLC), Glutathione S-transferase Mu 1 (GSTM1), Glutathione S-transferase Theta 1 (GSTT1), and Glutathione S-transferase P1 (GSTP1), which have been associated to the GSH metabolic pathway and CF clinical severity.
  
  
  METHODS
  A total of 180 CF's patients were included in this study, which investigated polymorphisms in GCLC and GST genes (GCLC -129C>T and -3506A>G; GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G) by PCR and PCR-RFLP associating to clinical variables of CF severity, including variables of sex, clinical scores [Shwachman-Kulczycki, Kanga e Bhalla (BS)], body mass index, patient age, age for diagnosis, first clinical symptoms, first colonization by Pseudomonas aeruginosa, sputum's microorganisms, hemoglobin oxygen saturation in the blood, spirometry and comorbidities. The CFTR genotype was investigated in all patients, and the genetic interaction was performed using MDR2.0 and MDRPT0.4.7 software.
  
  
  RESULTS
  The analysis of multiple genes in metabolic pathways in diseases with variable clinical expression, as CF disease, enables understanding of phenotypic diversity. Our data show evidence of interaction between the GSTM1 and GSTT1 genes deletion, and GSTP1*+313A>G polymorphism with CFTR gene mutation classes, and BS (Balance testing accuracy=0.6824, p=0.008), which measures the commitment of bronchopulmonary segments by tomography.
  
  
  CONCLUSIONS
  Polymorphisms in genes associated with metabolism of GSH act on the CF's severity.
authors.affiliation: Department of Pediatrics, Faculdade de Ciências Médicas, Universidade Estadual de Campinas-Unicamp, 13081-970, PO Box: 6111, Campinas, SP, Brazil. fernandolimamarson@hotmail.com
authors.forename: Fernando Augusto
authors.initials: FA
authors.lastname: de Lima Marson
authors.forename: Carmen Sílvia
authors.initials: CS
authors.lastname: Bertuzzo
authors.forename: Rodrigo
authors.initials: R
authors.lastname: Secolin
authors.forename: Antônio Fernando
authors.initials: AF
authors.lastname: Ribeiro
authors.forename: José Dirceu
authors.initials: JD
authors.lastname: Ribeiro
mesh_terms: D000293:Adolescent; D000328:Adult; D015992:Body Mass Index; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D005260:Female; D060045:Genes, Modifier; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D007223:Infant; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D009154:Mutation; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D012720:Severity of Illness Index; D012984:Software; D055815:Young Adult
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D005721:Glutamate-Cysteine Ligase; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C505032:CFTR protein, human; C413545:glutathione S-transferase T1; C496556:GSTP1 protein, human; C546365:GCLM protein, human