title: Mannose-binding lectin gene as a modifier of the cystic fibrosis phenotype in Argentinean pediatric patients.
abstract: BACKGROUND
  There is a considerable variation in the phenotype and course of the disease in cystic fibrosis (CF) even in patients with the same CFTR genotype, suggesting that other factors are important for prognosis. Mannose-binding lectin (MBL) has been proposed as one of these factors. We therefore investigated the influence of MBL2 gene variants on disease severity, age at acquisition of Pseudomonas aeruginosa, and survival in CF patients.
  
  
  METHODS
  MBL2 variants were studied in 106 Argentinean pediatric CF patients carrying two severe CFTR mutations. Clinical phenotype was defined according to the Shwachman score and lung function tests. Age at infection with P. aeruginosa and age at death were also recorded.
  
  
  RESULTS
  MBL insufficiency was associated with a 3.5-fold risk of having a severe phenotype (CI 95%: 1.2-10.3, p=0.03). It was also associated with an earlier onset of infection with P. aeruginosa (p=0.035). No statistically significant differences were found in FEV1 and survival.
  
  
  CONCLUSIONS
  MBL insufficiency was associated with detrimental progression of the disease. These results together with previous findings suggest that the effect of MBL2 expression may be a major determinant of the severity of the clinical phenotype in patients with CF.
authors.affiliation: Laboratorio de Biología Molecular, Servicio de Genética, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina.
authors.forename: Luis Pablo
authors.initials: LP
authors.lastname: Gravina
authors.affiliation: Laboratorio de Biología Molecular, Servicio de Genética, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina.
authors.forename: Carolina
authors.initials: C
authors.lastname: Crespo
authors.affiliation: Servicio de Neumonología, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina.
authors.forename: Hilda
authors.initials: H
authors.lastname: Giugno
authors.affiliation: Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", CONICET, Buenos Aires, Argentina.
authors.forename: Luisa
authors.initials: L
authors.lastname: Sen
authors.affiliation: Laboratorio de Biología Molecular, Servicio de Genética, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina.
authors.forename: Lilien
authors.initials: L
authors.lastname: Chertkoff
authors.affiliation: Laboratorio de Biología Celular y Retrovirus, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", CONICET, Buenos Aires, Argentina.
authors.forename: Andrea
authors.initials: A
authors.lastname: Mangano
authors.affiliation: Servicio de Neumonología, Hospital de Pediatría "Prof. Dr. Juan P. Garrahan", Buenos Aires, Argentina.
authors.forename: Claudio
authors.initials: C
authors.lastname: Castaños
mesh_terms: D001118:Argentina / Q000453:epidemiology; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D003550:Cystic Fibrosis / Q000235:genetics* / Q000401:mortality / Q000503:physiopathology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics; D018450:Disease Progression; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D053208:Kaplan-Meier Estimate; D008297:Male; D037601:Mannose-Binding Lectin / Q000235:genetics*; D010641:Phenotype; D011110:Polymorphism, Genetic; D012129:Respiratory Function Tests; D012189:Retrospective Studies; D018570:Risk Assessment; D012720:Severity of Illness Index; D015996:Survival Rate
chemical_list: C445619:MBL2 protein, human; D037601:Mannose-Binding Lectin; D019005:Cystic Fibrosis Transmembrane Conductance Regulator
keywords: Cystic fibrosis; MBL2; Mannose-binding lectin; Modifier gene; Phenotype; Polymorphism