Exploration of interethnic variation and repurposed drug efficacy in the treatment of SARS-CoV-2 Infection (COVID-19)
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Abstract
The COVID-19 global pandemic has led to repurposing of drugs, with little underlying evidence for treatment safety and efficacy. This may increase complications for patients with acute viral respiratory infections. UGT1A1 and CYP2D6 enzymes are involved in the metabolism of atazanavir and fluvoxamine repurposed for COVID-19. This study aimed to elucidate the role of interethnic variation in these enzymes in the efficacy of repurposed drug therapies. A retrospective cohort of 101 Jordanian Arab samples were genotyped using Affymetrix DMET Plus Premier Package. Comprehensive global population genetic structure analyses were performed for CYP2D6 and UGT1A1 allele frequencies across multi-ethnic populations of over 131,000 global subjects from 417 published reports, revealing that Jordanian Arabs share the closest sequence homology to European and Near East populations. The East Asian populations have significantly over-representaiton of individuals with diplotype pairs for reduced atazanavir metabolism compared to the African populations and are more likely to show impaired UGT1A1 metabolism. East Asian populations are also 4.4x more likely to show impaired fluvoxamine metabolism than South Central Asian and Oceanian populations, and 8x more likely than other ancestry populations. The results here support previous findings that interethnic variation should be used for developing proper population-specific dosage guidelines.
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SciScore for 10.1101/2021.03.07.21253095: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: After a signed informed consent, a 3 ml venous blood sample was collected in 3 ml EDTA tubes from each participant at the Princess Haya Biotechnology Centre between May 2010 and December 2011.
IRB: Ethics approvals was provided by the Institutional Review Board (IRB) of the Jordan University of Science and Technology (registration number 67/2/2013), and performed in accordance with the principles enshrined in the Declaration of Helsinki.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Sample collection: This study retrospectively included 101 unrelated Jordanian participants, of which 56 were male … SciScore for 10.1101/2021.03.07.21253095: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement Consent: After a signed informed consent, a 3 ml venous blood sample was collected in 3 ml EDTA tubes from each participant at the Princess Haya Biotechnology Centre between May 2010 and December 2011.
IRB: Ethics approvals was provided by the Institutional Review Board (IRB) of the Jordan University of Science and Technology (registration number 67/2/2013), and performed in accordance with the principles enshrined in the Declaration of Helsinki.Randomization not detected. Blinding not detected. Power Analysis not detected. Sex as a biological variable Sample collection: This study retrospectively included 101 unrelated Jordanian participants, of which 56 were male and 45 were female. Table 2: Resources
Software and Algorithms Sentences Resources Statistical and genetic analyses were performed for selection and validation using Microsoft Excel and SPSS v16 (Fig. 4). Microsoft Excelsuggested: (Microsoft Excel, RRID:SCR_016137)SPSSsuggested: (SPSS, RRID:SCR_002865)These were implemented with the HWChisq and HWextact functions in HardyWeinberg R package34. HardyWeinbergsuggested: NoneDivergences were visualized by multidimensional scaling analysis (MDS) using the metaMDS function in the vegan R package (Table S4)36. vegansuggested: (vegan, RRID:SCR_011950)Furthermore, this biogeographic grouping system meets a key need in pharmacogenetics research by enabling consistent communication of the scale of variability in global allele frequencies and are now used by PharmGKB and CPIC. PharmGKBsuggested: (PharmGKB, RRID:SCR_002689)Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).
Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.Results from TrialIdentifier: No clinical trial numbers were referenced.
Results from Barzooka: We did not find any issues relating to the usage of bar graphs.
Results from JetFighter: We did not find any issues relating to colormaps.
Results from rtransparent:- Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
- No funding statement was detected.
- No protocol registration statement was detected.
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