title: Genetic variations in inflammatory mediators influence lung disease progression in cystic fibrosis.
abstract: The clinical course of cystic fibrosis (CF) varies considerably among patients carrying the same CF-causing gene mutation. Additional genetic modifiers may contribute to this variability. As airway inflammation is a key component of CF pathophysiology, we investigated whether major cytokine variants represent such modifiers in young CF patients. We tested 13 polymorphisms in 8 genes that play a key role in the inflammatory response: tumor necrosis factor, lymphotoxin alpha, interleukin (IL) 1B, IL1 receptor antagonist, IL6, IL8, IL10 and transforming growth factor beta 1 (TGFB1), for an association with lung disease progression and nutritional status in 329 CF patients. Variants in the TGFB1 gene at position +869T/C demonstrated a significant association with lung function decline. A less pronounced rate of decline in forced expiratory volume in 1 sec (FEV(1)) and forced vital capacity (FVC) were observed in patients heterozygous for TGFB1 +869 (+869CT), when compared to patients carrying either TGFB1 +869TT or +869CC genotypes. These findings support the concept that TGFB1 gene variants appear to be important genetic modifiers of lung disease progression in CF.
authors.affiliation: AP-HP, Hôpital Trousseau, Pediatric Pulmonary Department, Paris, France. harriet.corvol@trs.aphp.fr
authors.forename: Harriet
authors.initials: H
authors.lastname: Corvol
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Boelle
authors.forename: Jacques
authors.initials: J
authors.lastname: Brouard
authors.forename: Nicola
authors.initials: N
authors.lastname: Knauer
authors.forename: Katarina
authors.initials: K
authors.lastname: Chadelat
authors.forename: Alexandra
authors.initials: A
authors.lastname: Henrion-Caude
authors.forename: Cyril
authors.initials: C
authors.lastname: Flamant
authors.forename: Celine
authors.initials: C
authors.lastname: Muselet-Charlier
authors.forename: Michele
authors.initials: M
authors.lastname: Boule
authors.forename: Brigitte
authors.initials: B
authors.lastname: Fauroux
authors.forename: Christelle
authors.initials: C
authors.lastname: Vallet
authors.forename: Josue
authors.initials: J
authors.lastname: Feingold
authors.forename: Felix
authors.initials: F
authors.lastname: Ratjen
authors.forename: Hartmut
authors.initials: H
authors.lastname: Grasemann
authors.forename: Annick
authors.initials: A
authors.lastname: Clement
mesh_terms: D000293:Adolescent; D002648:Child; D003550:Cystic Fibrosis / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D014644:Genetic Variation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D007375:Interleukin-1 / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D008233:Lymphotoxin-alpha / Q000235:genetics; D008297:Male; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
chemical_list: D018836:Inflammation Mediators; D007375:Interleukin-1; D015850:Interleukin-6; D016209:Interleukin-8; D008233:Lymphotoxin-alpha; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10