INTERNATIONAL CONGRESS OF
PharmacoGenetics
A review of MT-RNR1 gene mutations associated with nonsyndromic hearing impairment due to aminoglycoside antibiotic usage
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Nastaran Bozorgi,1,*
1. Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Iran
- Introduction: Aminoglycosides are a class of antibiotics produced by soil actinomycetes. They treat infections caused by Gram-negative bacteria such as E.coli, Salmonella, and Klebsiella. These antibiotics are effective for individuals infected with bacterial strains that are resistant to multiple drugs, as well as for AIDS patients co-infected with tuberculosis and those with kidney (fibrocystic) patients. Types of aminoglycoside antibiotics include neomycin, streptomycin, gentamicin, and netilmicin. This class of antibiotics works by binding to the 16S rRNA of the bacterial small ribosomal subunit at the A site of mRNA, disrupting protein synthesis. According to the "endosymbiotic theory," the ribosome and 16S rRNA in bacteria are analogous to eukaryotic mitochondria and 12S rRNA in humans. These organelles are responsible for oxidative mechanisms. Despite some differences, such as the resistance of human mitochondria to antibiotics due to a double membrane and an allelic substitution in the aminoglycoside binding site of rRNA compared to bacterial ribosomes, research has shown that mutations in the MT-RNR1 gene can lead to the "nonsyndromic deafness" phenotype in individuals using this class of drugs. Hearing loss can significantly impact a person's life at any age. however, if it occurs in infancy before speech development, it can cause irreversible damage. Therefore, it is essential to implement personalized medicine and select appropriate treatment methods at the molecular level with high precision. This study aims to investigate genetic changes in the MT-RNR1 gene that result in aminoglycoside toxicity and subsequent hearing impairment.
- Methods: Keywords like MT-RNR1, nonsyndromic hearing impairment, and aminoglycoside antibiotics were used to search scientific databases such as Google Scholar and PubMed. This led to the selection and review of relevant articles.
- Results: Research in pharmacogenetics has shown that people's responses to drugs can vary significantly based on their genotype and specific genomic changes. Pharmacogenetics studies the effects of these genetic variations on drug responses. Research has shown that certain mutations in the MT-RNR1 gene are associated with the harmful effects of aminoglycoside antibiotics. This mutation is often inherited maternally, as indicated by family tree analysis. Hearing loss caused by the use of aminoglycoside antibiotics has been observed in diverse populations around the world. The severity of hearing loss is categorized as follows: mild (26-40 dB HL), moderate (41-55 dB HL), moderately severe (56-70 dB HL), severe (71-90 dB HL), and profound (greater than 91 dB HL). In individuals with normal hearing, the softest perceivable sound is 0 dB. The 1555A>G mutation (rs267606617) in the MT-RNR1 gene is prevalent in 33-5% of patients who experience aminoglycoside-induced deafness. It is associated with the development of bilateral hearing loss, which can range from severe to profound or mild to moderate. Another significant mutation is the 1494C>T (rs267606619) variant, which occurs in approximately 5% of affected individuals and also leads to bilateral hearing loss, which can vary in severity from mild to profound. There is a less common variant, 1095T>C (rs267606618), associated with moderate to profound hearing loss. Less common variations are 827A>G (rs28358569) and a deletion at position 961 (T deletion with various C insertions). People with these genetic differences may experience problems in cellular respiration because bacterial ribosomes and human mitochondrial ribosomes have similar structures. This can affect mitochondrial protein production, lower energy levels, and ultimately result in apoptosis, leading to deafness.
- Conclusion: Genetic testing and screening can help doctors identify the genetic makeup of individuals, which can prevent negative reactions to antibiotics and ensure the right medications are prescribed. While pharmacogenetic testing is needed for antibiotic treatment, There are challenges such as limited healthcare resources, high costs, time-consuming processes, complex interpretation of test results, and ethical concerns about how genetic information is used (such as its impact on insurance coverage). Also, because different people respond differently to the same drug doses, ongoing research across diverse populations and a wider range of antibiotics is necessary. The interpretation of pharmacogenetic test results can lead to the development of personalized medical strategies, which can improve antibiotic treatment by choosing the right antimicrobial agent, adjusting the dosage for each individual, and minimizing side effects.
- Keywords: MT-RNR1, nonsyndromic hearing impairment, aminoglycoside antibiotics
