Combined DPD and UGT1A1 Mutation in a Single Patient: A Case Report

Abstract

Pharmacogenetic studies on 5-FU have mostly focused on enzyme Dihydropyrimidine Dehydrogenase (DPD), which is a rate-limiting enzyme in uracil and thymine catabolic pathway. Its activity has been found to be highly variable in different populations and several DPYD polymorphisms have been reported to be responsible for the decrease in activity of enzyme function and a high risk of 5-FU toxicity. Studies on 5-FU have mostly focused on t UGT1A1 genetic variations have been extensively investigated in relation to hyperbilirubinemia syndromes, as the UGT1A1 enzyme catalyses bilirubin glucuronidation. The importance of glucuronidation pathway in irinotecan treatment, UGT1A1 was chosen as the candidate gene to be investigated as a predictor of severe toxicity. Existence of combined mutation of DPD and UGT1A1 is adversely increases the treatment toxicity. A 57 year old male patient was diagnosed moderately differentiated adenocarcinoma rectum and patient was evaluated with DPD gene mutation and found positive for Heterozygous (496A19), Homozygous (855/C) and Heterozygous (1627). Thereafter, the treatment regimen was changed to IROX, patient’s conditions worsen progressively with Grade IV neutropenia and further complicated by sepsis. Patient was evaluated for UGT1A1 gene mutation. Subsequently, UGT1A1*1 and UGT1A1*28 gene was found to be mutated (Heterozygous). UGT1A1