Impact of polymorphism of Multidrug Resistance-associated Protein 1 (ABCC1) gene on the severity of cystic fibrosis

J Cyst Fibros. 2011 Jul;10(4):228-33. doi: 10.1016/j.jcf.2010.10.007. Epub 2011 Mar 24.

Abstract

A 5'FR/G-260C (NCBI reference: 010393.16:g.15983174C>G) functional polymorphism of Multidrug Resistance-associated Protein 1 (ABCC1) promoter has been reported which influences ABCC1 expression including inflammatory related events. We aimed at investigating the impact of this polymorphism on the severity of CF disease. In this multicentric study, key clinical features of 203 CF patients homozygous for the F508del mutation were recorded. Kaplan-Meier analysis showed that patients with the rare CC genotype were chronically colonized by PA around 6 years earlier (mean ± SD: 11.2 year ± 7.8, 95% CI for the mean: 5.7-16.8) than those with the GG or the CG alleles (p<=0.01) and a FEV1 <60% predicted was first observed earlier in this group (p<0.05). Concordant trends to better nutritional status and FEV1 were observed in the slightly older GG subgroup. The potential role of ABCC1 promoter as a modifier gene deserves further study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Cell Line
  • Cystic Fibrosis / epidemiology
  • Cystic Fibrosis / genetics*
  • Cystic Fibrosis / microbiology
  • Databases, Factual
  • Epithelial Cells / cytology
  • Female
  • Gene Frequency
  • Genotype
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Multidrug Resistance-Associated Proteins / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Promoter Regions, Genetic / genetics
  • Pseudomonas Infections / epidemiology
  • Pseudomonas Infections / genetics*
  • Pseudomonas aeruginosa / isolation & purification*
  • Severity of Illness Index
  • Young Adult

Substances

  • Multidrug Resistance-Associated Proteins
  • multidrug resistance-associated protein 1