Frequency of mitochondrial 12S ribosomal RNA variants in an adult cystic fibrosis population

Pharmacogenet Genomics. 2008 Dec;18(12):1095-102. doi: 10.1097/FPC.0b013e328312b072.


In adult cystic fibrosis patient populations, gram-negative bacteria, particularly Pseudomonas aeruginosa, frequently require aggressive therapy including systemic antibiotics, bronchodilators and airway clearance techniques. Aminoglycosides including tobramycin are used frequently to control these chronic airway infections. They, however, cause important nephrotoxic and ototoxic effects that can significantly alter the quality of life. We investigated the genetic predisposition to aminoglycoside ototoxicity in a typical unscreened North American cystic fibrosis population by screening for variants in mitochondrial 12S ribosomal RNA and noted several polymorphisms occurred at higher frequencies than expected and were associated with clinically significant cases of hearing loss. In the population studied, both patients possessing the 1555A>G transition exhibited profound ototoxicity after nontoxic dosing of tobramycin. We also identified new homoplasmic genetic variations in the mitochondrial 12S ribosomal RNA, several of which occurred in highly conserved regions of the gene and were present in patients with moderate-to-severe ototoxicity after exposure to aminoglycosides.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Audiometry, Pure-Tone
  • Base Sequence
  • Conserved Sequence
  • Cystic Fibrosis / genetics*
  • DNA-Binding Proteins / genetics
  • Demography
  • Female
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Mitochondria / genetics*
  • Molecular Sequence Data
  • Mutation / genetics*
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • RNA, Ribosomal / genetics*
  • Transcription Factors / genetics


  • DNA-Binding Proteins
  • NR4A2 protein, human
  • Nuclear Receptor Subfamily 4, Group A, Member 2
  • RNA, Ribosomal
  • RNA, ribosomal, 12S
  • Transcription Factors