A polymorphism in the 5' UTR of the DEFB1 gene is associated with the lung phenotype in F508del homozygous Italian cystic fibrosis patients

Sergio Crovella, Ludovica Segat, Annalisa Amato, Emmanouil Athanasakis, Valentino Bezzerri, Cesare Braggion, Rosaria Casciaro, Giuseppe Castaldo, Carla Colombo, Angela Elvira Covone, Virginia De Rose, Rolando Gagliardini, Carmen Lanzara, Laura Minicucci, Marcello Morgutti, Elena Nicolis, Francesca Pardo, Serena Quattrucci, Valeria Raia, Roberto RavazzoloManuela Seia, Valentino Stanzial, Lisa Termini, Laura Zazzeron, Giulio Cabrini, Paolo Gasparini

Research output: Contribution to journalArticlepeer-review


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 (59 UTR> of the b 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, ns50) or severe lung phenotype patients (Sp, ns42). 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 (ORs0.48 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.

Original languageEnglish
Pages (from-to)49-54
Number of pages6
JournalClinical Chemistry and Laboratory Medicine
Issue number1
Publication statusPublished - Jan 2011


  • Cystic fibrosis
  • DEFB1
  • Functional SNPs
  • Innate immunity
  • Lung phenotype
  • Modifier genes

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Biochemistry, medical


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