Genetic determinants of airways' colonisation with Pseudomonas aeruginosa in cystic fibrosis

Lancet. 1993 Jan 23;341(8839):189-93. doi: 10.1016/0140-6736(93)90062-l.

Abstract

Exocrine pancreatic insufficiency and lung infection with Pseudomonas aeruginosa are major features of cystic fibrosis (CF). This monogenic disease is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. 267 children and adolescents with CF who were regularly seen at the same centre were assessed for an association of the CFTR mutation genotype with exocrine pancreatic function and the age of onset of chronic colonisation with P aeruginosa. The major mutation delta F508 accounted for 74% of CF alleles; 33 further CFTR mutations had been detected on the CF chromosomes of the study population by June, 1992. With the exception of delta F508/R347P compound heterozygotes, patients of the same mutation genotype were either pancreas insufficient (PI) or pancreas sufficient (PS). The age-specific colonisation rates with P aeruginosa were significantly lower in PS than in PI patients. The missense and splice site mutations that are "mild" CF alleles with respect to exocrine pancreatic function were also "low risk" alleles for the acquisition of P aeruginosa. On the other hand, the proportion of P aeruginosa-positive patients increased most rapidly in the PI delta F508 compound heterozygotes who were carrying a termination mutation in the nucleotide binding fold-encoding exons. Pancreatic status and the risk of chronic airways' colonisation with P aeruginosa are predisposed by the CFTR mutation genotype and can be differentiated by the type and location of the mutations in the CFTR gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Causality
  • Child
  • Child, Preschool
  • Chronic Disease
  • Colony Count, Microbial
  • Cystic Fibrosis / classification
  • Cystic Fibrosis / complications
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Evaluation Studies as Topic
  • Female
  • Gene Frequency
  • Genotype
  • Germany / epidemiology
  • Heterozygote
  • Homozygote
  • Humans
  • Incidence
  • Infant
  • Male
  • Membrane Proteins / genetics*
  • Mutation / genetics*
  • Outpatient Clinics, Hospital
  • Proportional Hazards Models
  • Pseudomonas Infections / epidemiology
  • Pseudomonas Infections / etiology
  • Pseudomonas Infections / microbiology*
  • Respiratory Tract Infections / epidemiology
  • Respiratory Tract Infections / etiology
  • Respiratory Tract Infections / microbiology*

Substances

  • CFTR protein, human
  • Membrane Proteins
  • Cystic Fibrosis Transmembrane Conductance Regulator