UGT1A1 Regulatory Variant with Potential Effect on Efficacy of HIV and Cancer Drugs Commonly Prescribed in South Africa

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::

• Dolutegravir
• eQTL
• Irinotecan
• South Africa
• UGT1A1

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.

Additional information

Funding

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