Frequency of mitochondrial 12S ribosomal RNA variants in an adult cystic fibrosis population
| Autor: | Colleen Eckhardt, Antine E. Stenbit, Douglas Conrad, Erika M. Zettner, Ivan Wick, Gary Hardiman |
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| Rok vydání: | 2008 |
| Předmět: |
Adult
Male medicine.medical_specialty Cystic Fibrosis Genotype Molecular Sequence Data Population Biology medicine.disease_cause MT-RNR1 Cystic fibrosis Ototoxicity Internal medicine Nuclear Receptor Subfamily 4 Group A Member 2 Genetics medicine Tobramycin Genetic predisposition Humans General Pharmacology Toxicology and Pharmaceutics education Molecular Biology Conserved Sequence Genetics (clinical) Demography education.field_of_study Base Sequence Pseudomonas aeruginosa Aminoglycoside Middle Aged medicine.disease Mitochondria DNA-Binding Proteins Endocrinology RNA Ribosomal Mutation Immunology Audiometry Pure-Tone Molecular Medicine Female Transcription Factors medicine.drug |
| Zdroj: | Pharmacogenetics and Genomics. 18:1095-1102 |
| ISSN: | 1744-6872 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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