Polymorphisms in the glutathione pathway modulate cystic fibrosis severity: a cross-sectional study
1 Center for Investigation in Pediatrics, Faculty of Medical Sciences, University of Campinas. Tessália Vieira de Camargo, 126. Cidade Universitária “Zeferino Vaz”, CEP: 13083-887 Campinas, São Paulo, Brazil
2 Department of Medical Genetics, Faculty of Medical Sciences, University of Campinas. Tessália Vieira de Camargo, 126. Cidade Universitária “Zeferino Vaz”, CEP: 13083-887 Campinas, São Paulo, Brazil
BMC Medical Genetics 2014, 15:27 doi:10.1186/1471-2350-15-27Published: 4 March 2014
Cystic fibrosis (CF) clinically manifests with various levels of severity, which are thought to be modulated by mutations in the cystic fibrosis transmembrane conductance regulator gene (CFTR), modifier genes, and the environment. This study verified whether polymorphisms in modifier genes associated with glutathione (GSH) metabolism influence CF severity.
A cross-sectional study of 180 CF patients was carried out from 2011 to 2012. We analyzed CFTR mutations, polymorphisms (GSTM1 and GSTT1 deletions, GSTP1 + 313A > G, GCLC-129C > T, and GCLC-3506A > G) in modifier genes and CF clinical severity as assessed by 28 clinical and laboratory variables.
Significant associations were found between modifier gene polymorphisms and particular phenotypes or genotype changes. These included GCLC-129C > T with a higher frequency of the Pseudomonas aeruginosa mucoid to CC genotype (p = 0.044), and GCLC-3506A > G with a higher frequency of the no-mucoid P. aeruginosa (NMPA) to AA genotype (p = 0.012). The GSTT1 deletion was associated with a higher frequency of the NMPA to homozygous deletion (p = 0.008), GSTP1 + 313A > G with a minor risk of osteoporosis (p = 0.036), and patient age ≤ 154 months (p = 0.044) with the AA genotype. The Bhalla score was associated with GCLC-3506A > G (p = 0.044) and GSTM1/GSTT1 deletion polymorphisms (p = 0.02), while transcutaneous hemoglobin oxygen saturation levels were associated with GSTT1 deletions (p = 0.048).
CF severity is associated with polymorphisms in GSH pathways and CFTR mutations.