Short Communication

UGT1A1 regulatory variant with potential effect on efficacy of HIV and cancer drugs commonly prescribed in South Africa

Division of Human Genetics, National Health Laboratory Service, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa

Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa

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Phelelani Thokozani Mpangase

https://orcid.org/0000-0001-8280-8940

Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa

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Dhriti Sengupta

https://orcid.org/0000-0001-6315-7804

Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa

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Stanford Kwenda

https://orcid.org/0000-0002-9008-4898

Sequencing Core Facility, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, 2192, South Africa

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Demetra Mavri-Damelin

https://orcid.org/0000-0003-3255-4684

School of Molecular & Cell Biology, Faculty of Science, University of the Witwatersrand, Johannesburg, 2050, South Africa

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Michèle Ramsay

*Author for correspondence:

E-mail Address: Michele.Ramsay@wits.ac.za

https://orcid.org/0000-0002-4156-4801

Division of Human Genetics, National Health Laboratory Service, School of Pathology, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2000, South Africa

Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, 2050, South Africa

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Published Online:16 Sep 2021https://doi.org/10.2217/pgs-2021-0062

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Abstract

Aim: Despite the high disease burden of human immunodeficiency virus (HIV) infection and colorectal cancer (CRC) in South Africa (SA), treatment-relevant pharmacogenetic variants are understudied. Materials & methods: Using publicly available genotype and gene expression data, a bioinformatic pipeline was developed to identify liver expression quantitative trait loci (eQTLs). Results: A novel cis-eQTL, rs28967009, was identified for UGT1A1, which is predicted to upregulate UGT1A1 expression thereby potentially affecting the metabolism of dolutegravir and irinotecan, which are extensively prescribed in SA for HIV and colorectal cancer treatment, respectively. Conclusion: As increased UGT1A1 expression could affect the clinical outcome of dolutegravir and irinotecan treatment by increasing drug clearance, patients with the rs28967009A variant may require increased drug doses to reach therapeutic levels or should be prescribed alternative drugs.

Keywords:

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Vol. 22, No. 15

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Received 20 May 2021

Accepted 23 August 2021

Published online 16 September 2021

Published in print October 2021

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Financial & competing interests disclosure

JM Mathew was supported by a grant holder linked bursary from the South African National Research Foundation. M Ramsay is a South African Research Chair in Genomics and Bioinformatics of African populations hosted by the University of the Witwatersrand, funded by the Department of Science and Technology, and administered by the National Research Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

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