Please use this identifier to cite or link to this item: http://repositorio.unicamp.br/jspui/handle/REPOSIP/200675
Type: Artigo de periódico
Title: Genetic Interaction Of Gsh Metabolic Pathway Genes In Cystic Fibrosis.
Author: de Lima Marson, Fernando Augusto
Bertuzzo, Carmen Sílvia
Secolin, Rodrigo
Ribeiro, Antônio Fernando
Ribeiro, José Dirceu
Abstract: 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. 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. 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. Polymorphisms in genes associated with metabolism of GSH act on the CF's severity.
Subject: Adolescent
Adult
Body Mass Index
Child
Child, Preschool
Cross-sectional Studies
Cystic Fibrosis
Cystic Fibrosis Transmembrane Conductance Regulator
Female
Genes, Modifier
Genetic Predisposition To Disease
Genotype
Glutamate-cysteine Ligase
Glutathione S-transferase Pi
Glutathione Transferase
Humans
Infant
Male
Metabolic Networks And Pathways
Mutation
Polymerase Chain Reaction
Polymorphism, Genetic
Polymorphism, Restriction Fragment Length
Severity Of Illness Index
Software
Young Adult
Rights: fechado
Identifier DOI: 10.1186/1471-2350-14-60
Address: http://www.ncbi.nlm.nih.gov/pubmed/23758905
Date Issue: 2013
Appears in Collections:Unicamp - Artigos e Outros Documentos

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