UGT1A1regulatory variant with potential effect on efficacy of HIV and cancer drugs commonly prescribed in South Africa

Autor: Mathew, Jenny Mary, Mpangase, Phelelani Thokozani, Sengupta, Dhriti, Kwenda, Stanford, Mavri-Damelin, Demetra, Ramsay, Michèle
Zdroj: Pharmacogenomics; 20210101, Issue: Preprints
Abstrakt: 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 UGT1A1expression 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 UGT1A1expression 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.
Databáze: Supplemental Index