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dc.contributor.authorRichardson, Marty
dc.contributor.authorKirkham, Jamie
dc.contributor.authorDwan, Kerry
dc.contributor.authorSloan, Derek J.
dc.contributor.authorDavies, Geraint
dc.contributor.authorJorgensen, Andrea L.
dc.date.accessioned2018-11-21T10:30:13Z
dc.date.available2018-11-21T10:30:13Z
dc.date.issued2018-11-20
dc.identifier.citationRichardson , M , Kirkham , J , Dwan , K , Sloan , D J , Davies , G & Jorgensen , A L 2018 , ' CYP genetic variants and toxicity related to anti-tubercular agents: a systematic review and meta-analysis ' , Systematic Reviews , vol. 7 , 204 . https://doi.org/10.1186/s13643-018-0861-zen
dc.identifier.issn2046-4053
dc.identifier.otherPURE: 256653507
dc.identifier.otherPURE UUID: c7e4899f-2aa0-4e58-8961-aca2d4bcf8b5
dc.identifier.otherRIS: urn:F88DB7584C9A6A3E18CE6A94993490FC
dc.identifier.otherRIS: Richardson2018
dc.identifier.otherScopus: 85056802978
dc.identifier.otherWOS: 000450865300005
dc.identifier.urihttp://hdl.handle.net/10023/16517
dc.descriptionMR is supported partly by Liverpool Reviews and Implementation Group (LRiG), based on funding from the National Institute for Health Research Health Technology Assessment Programme (URL, https://www.nihr.ac.uk/funding-and-support/funding-for-research-studies/funding-programmes/healthtechnology-assessment/), and partly by the Effective Health Care Research Consortium, which is funded by UKAid from the UK Government Department for International Development (Grant number, 5242; URL, https://www.gov.uk/government/organisations/department-for-international-development).en
dc.description.abstractBackground: Treatment with anti-tuberculosis drugs may cause patients to experience serious adverse effects. Genetic factors, such as polymorphisms of CYP genes, may increase the likelihood of a patient experiencing such adverse drug reactions. In this systematic review and meta-analysis, we synthesised evidence for associations between CYP genetic variants and anti-tuberculosis drug-related toxicity outcomes. Methods: We searched MEDLINE, PubMed, EMBASE, BIOSIS and Web of Science to identify relevant studies. We performed meta-analyses to obtain an effect estimate for each genetic variant on each outcome, and stratified all analyses by country. We qualitatively assessed the methodological quality of the included studies. Results: We included data from 28 distinct cohorts of patients in the review. We identified many areas of concern with regard to the quality of included studies. Patients with homozygous mutant-type or heterozygous genotype at the CYP2E1 RsaI polymorphism were significantly less likely to experience hepatotoxicity than patients with homozygous wild-type genotype (odds ratio [OR] = 0.75, 95% confidence interval [CI] 0.56–1.00; p = 0.047, I2 = 58.2%). No significant differences were observed for the CYP2E1 DraI and PstI polymorphisms. For the 96-bp deletion-insertion single-nucleotide polymorphism (SNP) of the CYP2E1 gene, homozygous mutant-type significantly increased hepatotoxicity risk compared with homozygous wild-type (OR = 8.20, 95% CI 1.38–48.68, I2 = 0%); no significant difference was observed for heterozygous genotype compared with homozygous wild-type (OR = 0.77, 95% CI 0.19–3.21, I2 = 0%). Conclusions: Generally, we identified that coverage of the association between SNPs of CYP genes and anti-tuberculosis drug-related toxicity outcomes is incomplete. We observed significant associations between the RsaI and 96-bp deletion-insertion SNPs of the CYP2E1 gene and anti-tuberculosis drug-related hepatotoxicity. We were unable to comment on the impact of ethnicity on the investigated associations, as information on participants’ ethnicity was sparsely reported in the included studies.
dc.format.extent15
dc.language.isoeng
dc.relation.ispartofSystematic Reviewsen
dc.rights© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.subjectTuberculosisen
dc.subjectPharmacogeneticsen
dc.subjectToxicityen
dc.subjectMeta-analysisen
dc.subjectRA0421 Public health. Hygiene. Preventive Medicineen
dc.subjectNDASen
dc.subject.lccRA0421en
dc.titleCYP genetic variants and toxicity related to anti-tubercular agents: a systematic review and meta-analysisen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Infection and Global Health Divisionen
dc.identifier.doihttps://doi.org/10.1186/s13643-018-0861-z
dc.description.statusPeer revieweden


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