Quantitative Contribution of rs75017182 to Dihydropyrimidine Dehydrogenase mRNA Splicing and Enzyme Activity
2017; Wiley; Volume: 102; Issue: 4 Linguagem: Inglês
10.1002/cpt.685
ISSN1532-6535
AutoresQian Nie, Shikshya Shrestha, E.J. Tapper, CS Trogstad‐Isaacson, Kelly J. Bouchonville, AM Lee, Rongqian Wu, Calvin R. Jerde, Zhiquan Wang, P Kubica, SM Offer, RB Diasio,
Tópico(s)Pancreatic and Hepatic Oncology Research
ResumoDihydropyrimidine dehydrogenase (DPD; DPYD gene) variants have emerged as reliable predictors of adverse toxicity to the chemotherapy agent 5-fluorouracil (5-FU). The intronic DPYD variant rs75017182 has been recently suggested to promote alternative splicing of DPYD. However, both the extent of alternative splicing and the true contribution of rs75017182 to DPD function remain unclear. In the present study we quantified alternative splicing and DPD enzyme activity in rs75017182 carriers utilizing healthy volunteer specimens from the Mayo Clinic Biobank. Although the alternatively spliced transcript was uniquely detected in rs75017182 carriers, canonically spliced DPYD levels were only reduced by 30% (P = 2.8 × 10
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