Referenced in: none

Automatically associated channels: Kir2.3

Title: Association between genetically determined pancreatic status and lung disease in adult cystic fibrosis patients.

Authors: Yann Loubières, Dominique Grenet, Brigitte Simon-Bouy, Jacques Medioni, Paul Landais, Claude Ferec, Marc Stern

Journal, date & volume: Chest, 2002 Jan , 121, 73-80

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/11796434

Abstract
The association between genotype and phenotype in cystic fibrosis (CF) has been clearly established for pancreatic status, but not for lung disease.Retrospective study.A respiratory unit of a teaching hospital.We studied 51 adult CF patients for whom current data and genotype were available. Thirty-seven patients carried two severe mutations associated with pancreatic insufficiency phenotype (group S). Fourteen patients carried at least one mild (and dominant) mutation associated with pancreatic sufficiency phenotype (group M).We compared the course of the disease between the two groups, looking for a genotype/phenotype association for lung disease.The mean age of the population was 30 years. Patients with two severe mutations presented more severe disease with earlier onset (1.7 years vs 7.9 years, p = 0.0001). They presented with a more severe respiratory impairment, with a lower mean FEV(1) (29% of predictive value vs 58% of predictive value, p < 0.001); a higher Pseudomonas colonization rate (97% vs 57%, p < 0.01); a more frequent end-stage respiratory insufficiency, defined by a FEV(1) < 30% (73% vs 29%, p < 0.05); and a more marked yearly decline of FEV(1) (3% vs 1.4%, p < 0.001). By multivariate logistic regression analysis, carrying two severe mutations was the only independent predictor of a terminal respiratory insufficiency (relative risk, 6.75; 95% confidence interval, 1.79 to 26.50; p = 0.003).This study suggests that pulmonary disease appears to be associated with the severity of CF transmembrane regulator mutations.