MOLGEN: DPYD Variant

Status: Open

Specialty: Multiple ()

Date Opened: 19/Oct/2023

Planned Close Date: 30/Apr/2026

Sponsor:  University of Liverpool

Principal Investigator: Dr Moon

Study Title: Molecular genetics of adverse drug reactions: from candidate genes to genome wide association studies 

Our study aims to recruit participants who have experienced an Adverse Drug Reaction (ADR) to any drug.  As part of the study, we will collect a small blood or saliva sample from the participants to conduct genetic analysis. One specific ADR we are investigating is caused by a deficiency in the enzyme Dihydropyrimidine dehydrogenase (DPD), which is responsible for breaking down anticancer drugs such as 5-fluorouracil (5FU), capecitabine, and tegafur. 

A deficiency of this enzyme, either complete or partial, can result in the inadequate breakdown of these drugs, leading to increased toxicity and potential harm to the bone marrow. In some cases, this has even resulted in severe toxicity and death in patients receiving these drugs. However, if a patient is found to have a genetic deficiency in DPD, a dose alteration may be possible, reducing the likelihood of bone marrow suppression and other toxicities associated with the treatment. 

Currently, prior to prescribing 5FU, all patients in the NHS undergo routine testing for four variants of the DPD gene, and doses are adjusted accordingly to prevent toxicity. The purpose of our research is to identify any additional variants across diverse ancestral populations 

To achieve this, samples are tested using genotyping methods. While the four variants routinely tested for are largely associated with European populations, there is limited literature on DPD deficiency in non-European populations. As a result, non-European populations are typically treated as wild type and prescribed the conventional dose, which puts them at higher risk of toxicity. By testing for variants in non-European populations, we may be able to identify new variants that affect these populations.