{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T02:35:27Z","timestamp":1790044527431,"version":"4.0.1"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"7","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["GNT1194694"],"award-info":[{"award-number":["GNT1194694"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Aminoglycosides (AGs) are important antibiotics in the treatment of Gram-negative sepsis. However, they are associated with the risk of irreversible sensorineural hearing loss (SNHL). Several genetic variants have been implicated in the development of ototoxicity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>To evaluate the pharmacogenetic determinants of AG-related ototoxicity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>This study followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses and was registered on Prospero (CRD42022337769). In Dec 2022, PubMed, Cochrane Library, Embase and MEDLINE were searched. Included studies were those reporting original data on the effect of the AG-exposed patient\u2019s genome on the development of ototoxicity.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Of 10\u200a202 studies, 31 met the inclusion criteria. Twenty-nine studies focused on the mitochondrial genome, while two studied the nuclear genome. One study of neonates found that 30% of those with the m.1555A\u200a&amp;gt;\u200aG variant failed hearing screening after AG exposure (level 2 evidence). Seventeen additional studies found the m.1555A\u200a&amp;gt;\u200aG variant was associated with high penetrance (up to 100%) of SNHL after AG exposure (level 3\u20134 evidence). Nine studies of m.1494C\u200a&amp;gt;\u200aT found the penetrance of AG-related SNHL to be up to 40%; however, this variant was also identified in those with SNHL without AG exposure (level 3\u20134 evidence). The variants m.1005T\u200a&amp;gt;\u200aC and m.1095T\u200a&amp;gt;\u200aC may be associated with AG-related SNHL; however, further studies are needed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>This review found that the m.1555A\u200a&amp;gt;\u200aG and m.1494C\u200a&amp;gt;\u200aT variants in the MT-RNR1 gene have the strongest evidence in the development of AG-related SNHL, although study quality was limited (level 2\u20134). These variants were associated with high penetrance of a SNHL phenotype following AG exposure.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkae106","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T18:58:29Z","timestamp":1713380309000},"page":"1508-1528","source":"Crossref","is-referenced-by-count":19,"title":["Pharmacogenetics of aminoglycoside-related ototoxicity: a systematic review"],"prefix":"10.1093","volume":"79","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1883-0571","authenticated-orcid":false,"given":"D","family":"Gaafar","sequence":"first","affiliation":[{"name":"Infectious Diseases and Clinical Pharmacology Units, Department of General Medicine, Royal Children\u2019s Hospital , Parkville , Australia"},{"name":"Department of Paediatrics, The University of Melbourne , 50 Flemington Rd, Parkville, VIC 3052 , Australia"},{"name":"Antimicrobials Group, Murdoch Children\u2019s Research Institute , Parkville , 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