Published ahead of print on May 11, 2006, doi:10.1164/rccm.200508-1281OC Am. J. Respir. Crit. Care Med., Volume 174, Number 4, August 2006, 415-419 A more recent version of this article appeared on August 15, 2006
Submitted on August 18, 2005 Variants in the Glutamate-Cysteine-Ligase Gene are Associated with Cystic Fibrosis Lung DiseaseEdward F McKone1,1 Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA, 2 Department of Environmental and Occupational Health Sciences and Center for Ecogenetics and Environmental Health, University of Washington, Seattle, WA, USA, 3 UBC McDonald Research Laboratories/iCAPTURE Center, Vancouver, BC, Canada * To whom correspondence should be addressed. E-mail: tjkav{at}u.washington.edu.
Background: Chronic progressive lung disease is the most serious complication of cystic fibrosis (CF). Glutathione plays an important role in the protection of the CF lung against oxidant-induced lung injury. Objectives: We hypothesized that a polymorphism in a novel candidate gene that regulates glutathione synthesis might influence cystic fibrosis (CF) lung disease. Methods: In a cross-sectional study, subjects were recruited from CF clinics in Seattle and multiple centers in Canada. We tested for an association between CF lung disease and a functional polymorphism in the glutamate-cysteine ligase catalytic subunit (GCLC) gene. Multiple linear regression was used to test for association between polymorphisms of GCLC and severity of CF lung disease while adjusting for age, P. aeruginosa infection and CFTR genotype. Analysis was then repeated for CF patients stratified by CFTR genotype. Measurements and Main Results: Four hundred and forty CF subjects participated in the study (51% male, mean (SD) age=26±11 yrs, mean FEV1=62±28% predicted). In the total population, there was a trend towards an association between GCLC genotypes and CF lung disease (linear regression coefficient (SEM) = 1.68 (1.0), p=0.097). In the stratified analysis, there was a highly significant association between GCLC genotype and CF lung function in subjects with a milder CFTR genotype (linear regression coefficient (SEM) = 5.5 (1.7), p=0.001). Conclusions: In CF patients with a milder CFTR genotype, there is a strong association between functional polymorphisms of the GCLC gene and CF lung disease severity. Key words: Modifier genes, glutathione, CFTR genotype
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
