Association of MBL2, TGF-beta1 and CD14 gene polymorphisms with lung disease severity in cystic fibrosis

J Bras Pneumol. 2009 Apr;35(4):334-42. doi: 10.1590/s1806-37132009000400007.
[Article in English, Portuguese]

Abstract

Objective: To identify associations between genetic polymorphisms (in the MBL2, TGF-beta1 and CD14 genes) and the severity of the lung disease in patients with cystic fibrosis (CF), as well as between the presence of DeltaF508 alleles and lung disease severity in such patients.

Methods: This was a cross-sectional cohort study, based on clinical and laboratory data, involving 105 patients with CF treated at a university hospital in the 2005-2006 period. We included 202 healthy blood donors as controls for the determination of TGF-beta1 and CD14 gene polymorphisms. Polymorphisms in the MBL2 and TGF-beta1 genes at codon 10, position +869, were genotyped using the allele-specific PCR technique. The C-159T polymorphism in the CD14 gene was genotyped using PCR and enzymatic digestion.

Results: Of the 105 CF patients evaluated, 67 presented with severe lung disease according to the Shwachman score. The MBL2 gene polymorphisms were not associated with disease severity in the CF patients. Analysis of the T869C polymorphism in the TGF-beta1 gene showed an association only between TC heterozygotes and mild pulmonary disease. Although patients presenting the TT genotype of the C159T polymorphism in the CD14 gene predominated, there was no significant difference regarding lung disease severity.

Conclusions: There was an association between the TC genotype of the T869C polymorphism (TGF-beta1) and mild pulmonary disease in CF patients. In the CD14 gene, the TT genotype seems to be a risk factor for pulmonary disease but is not a modulator of severity. We found no association between being a DeltaF508 homozygote and presenting severe lung disease.

MeSH terms

  • Adult
  • Case-Control Studies
  • Cross-Sectional Studies
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Female
  • Genotype
  • Humans
  • Lipopolysaccharide Receptors / genetics*
  • Lung Diseases / genetics*
  • Male
  • Mannose-Binding Lectin / genetics*
  • Polymerase Chain Reaction
  • Polymorphism, Genetic*
  • Severity of Illness Index
  • Transforming Growth Factor beta1 / genetics*

Substances

  • Lipopolysaccharide Receptors
  • MBL2 protein, human
  • Mannose-Binding Lectin
  • Transforming Growth Factor beta1
  • cystic fibrosis transmembrane conductance regulator delta F508
  • Cystic Fibrosis Transmembrane Conductance Regulator