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- Ås, JoelUppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab (author)
Whole genome case-control study of central nervous system toxicity due to antimicrobial drugs
- Article/chapterEnglish2024
Publisher, publication year, extent ...
- Public Library of Science (PLoS),2024
- electronicrdacarrier
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- LIBRIS-ID:oai:DiVA.org:umu-222230
- https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222230URI
- https://doi.org/10.1371/journal.pone.0299075DOI
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-526190URI
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- Language:English
- Summary in:English
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- A genetic predisposition to central nervous system (CNS) toxicity induced by antimicrobial drugs (antibiotics, antivirals, antifungals, and antiparasitic drugs) has been suspected. Whole genome sequencing of 66 cases and 833 controls was performed to investigate whether antimicrobial drug-induced CNS toxicity was associated with genetic variation. The primary objective was to test whether antimicrobial-induced CNS toxicity was associated with seventeen efflux transporters at the blood-brain barrier. In this study, variants or structural elements in efflux transporters were not significantly associated with CNS toxicity. Secondary objectives were to test whether antimicrobial-induced CNS toxicity was associated with genes over the whole genome, with HLA, or with structural genetic variation. Uncommon variants in and close to three genes were significantly associated with CNS toxicity according to a sequence kernel association test combined with an optimal unified test (SKAT-O). These genes were LCP1 (q = 0.013), RETSAT (q = 0.013) and SFMBT2 (q = 0.035). Two variants were driving the LCP1 association: rs6561297 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51–8.46]) and the regulatory variant rs10492451 (p = 1.15x10-6, OR: 4.60 [95% CI: 2.51–8.46]). No common genetic variant, HLA-type or structural variation was associated with CNS toxicity. In conclusion, CNS toxicity due to antimicrobial drugs was associated with uncommon variants in LCP1, RETSAT and SFMBT2.
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- Bertulyte, IlmaUppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab(Swepub:uu)ilmbe876 (author)
- Norgren, NinaUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Department of Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Umeå University, Umeå, Sweden(Swepub:umu)niakan04 (author)
- Johansson, AnnaUppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylär evolution(Swepub:uu)anjoh226 (author)
- Eriksson, Niclas,1978-Uppsala universitet,Uppsala kliniska forskningscentrum (UCR),Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab(Swepub:uu)nieri103 (author)
- Green, HenrikDivision of Clinical Chemistry and Pharmacology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden; Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden,Linköping Univ, Dept Biomed & Clin Sci, Div Clin Chem & Pharmacol, Linköping, Sweden.;Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linköping, Sweden. (author)
- Wadelius, MiaUppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab(Swepub:uu)miawadel (author)
- Hallberg, Pär,1974-Uppsala universitet,Klinisk farmakogenomik och osteoporos,Science for Life Laboratory, SciLifeLab(Swepub:uu)pahal677 (author)
- Uppsala universitetKlinisk farmakogenomik och osteoporos (creator_code:org_t)
Related titles
- In:PLOS ONE: Public Library of Science (PLoS)19:21932-6203
Internet link
- https://doi.org/10.1371/journal.pone.0299075Fulltext
- https://umu.diva-portal.org/smash/get/diva2:1844729/FULLTEXT01.pdffulltext:print
- https://uu.diva-portal.org/smash/get/diva2:1849258/FULLTEXT01.pdffulltext:print
- https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-222230
- https://doi.org/10.1371/journal.pone.0299075
- https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-526190
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