title: A polymorphism in the 5' UTR of the DEFB1 gene is associated with the lung phenotype in F508del homozygous Italian cystic fibrosis patients.
abstract: BACKGROUND
  The identification of cystic fibrosis (CF) patients who are at greater risk of lung damage could be clinically valuable. Thus, we attempted to replicate previous findings and verify the possible association between three single nucleotide polymorphisms (SNPs c.-52G>A, c.-44C>G and c.-20G>A) in the 5' untranslated region (5' UTR) of the β defensin 1 (DEFB1) gene and the CF pulmonary phenotype.
  
  
  METHODS
  Genomic DNA from 92 Italian CF patients enrolled in different regional CF centres was extracted from peripheral blood and genotyped for DEFB1 SNPs using TaqMan(®) allele specific probes. In order to avoid genetic confounding causes that can account for CF phenotype variability, all patients were homozygous for the F508del CFTR mutation, and were then classified on the basis of clinical and functional data as mild lung phenotype (Mp, n=50) or severe lung phenotype patients (Sp, n=42).
  
  
  RESULTS
  For the c.-20G>A SNP, the frequency of the A allele, as well as the AA genotype, were significantly more frequent in Mp than in Sp patients, and thus this was associated with a protective effect against severe pulmonary disease (OR=0.48 and 0.28, respectively). The effect of the c.-20G>A A allele is consistent with a recessive model, and the protective effect against Sp is exerted only when it is present in homozygosis. For the other two SNPs, no differences were observed as allelic and genotypic frequency in the two subgroups of CF patients.
  
  
  CONCLUSIONS
  Our results, although necessary to be confirmed in larger and multiethnic populations, reinforce DEFB1 as a candidate modifier gene of the CF pulmonary phenotype.
authors.affiliation: Genetic Service, IRCCS Burlo Garofolo, Trieste, Italy. crovella@burlo.trieste.it
authors.forename: Sergio
authors.initials: S
authors.lastname: Crovella
authors.forename: Ludovica
authors.initials: L
authors.lastname: Segat
authors.forename: Annalisa
authors.initials: A
authors.lastname: Amato
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Athanasakis
authors.forename: Valentino
authors.initials: V
authors.lastname: Bezzerri
authors.forename: Cesare
authors.initials: C
authors.lastname: Braggion
authors.forename: Rosaria
authors.initials: R
authors.lastname: Casciaro
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Castaldo
authors.forename: Carla
authors.initials: C
authors.lastname: Colombo
authors.forename: Angela Elvira
authors.initials: AE
authors.lastname: Covone
authors.forename: Virginia
authors.initials: V
authors.lastname: De Rose
authors.forename: Rolando
authors.initials: R
authors.lastname: Gagliardini
authors.forename: Carmen
authors.initials: C
authors.lastname: Lanzara
authors.forename: Laura
authors.initials: L
authors.lastname: Minicucci
authors.forename: Marcello
authors.initials: M
authors.lastname: Morgutti
authors.forename: Elena
authors.initials: E
authors.lastname: Nicolis
authors.forename: Francesca
authors.initials: F
authors.lastname: Pardo
authors.forename: Serena
authors.initials: S
authors.lastname: Quattrucci
authors.forename: Valeria
authors.initials: V
authors.lastname: Raia
authors.forename: Roberto
authors.initials: R
authors.lastname: Ravazzolo
authors.forename: Manuela
authors.initials: M
authors.lastname: Seia
authors.forename: Valentino
authors.initials: V
authors.lastname: Stanzial
authors.forename: Lisa
authors.initials: L
authors.lastname: Termini
authors.forename: Laura
authors.initials: L
authors.lastname: Zazzeron
authors.forename: Giulio
authors.initials: G
authors.lastname: Cabrini
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
mesh_terms: D020121:5' Untranslated Regions; D000328:Adult; D003550:Cystic Fibrosis / Q000235:genetics*; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D005260:Female; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007558:Italy; D008297:Male; D009154:Mutation; D010641:Phenotype; D011110:Polymorphism, Genetic; D055815:Young Adult; D023083:beta-Defensins / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; C406407:DEFB1 protein, human; D023083:beta-Defensins; D019005:Cystic Fibrosis Transmembrane Conductance Regulator