DPD deficiency is an autosomal recessive metabolic disorder due to a decreased activity of the enzyme dihydropyrimidine dehydrogenase (DPD), an enzyme that catalyses the rate-limiting step in fluorouracil metabolism, encoded by the DPYD gene. Individuals who carry at least one copy of no-function DPYD variants, may not be able to metabolize fluorouracil at normal rates, and are at risk of potentially life-threatening fluorouracil toxicity. Drugs like 5-fluorouracil and capecitabine are used as chemotherapy drugs in the treatment of cancer patients. Of the genetic factors thought to contribute to fluoropyrimidine intolerance, the DPYD gene has been the most studied. This gene encodes the primary enzyme involved in breaking down fluoropyrimidines to inactive metabolites. Individuals who have a deficiency of the DPD enzyme have a significantly increased risk of suffering from severe fluoropyrimidine toxicity, and the stratification of patients on the basis of the DPYD genotype may help to prevent such adverse events. The prevalence of DPD deficiency in Caucasians is approximately 3%-5%. Symptomatic DPD deficiency is typically caused by homozygous inactivation of DPYD; whereas individuals who are heterozygotes tend to be asymptomatic. Signs of fluorouracil toxicity include severe diarrhea, severe mucositis, neutropenia, neurotoxicity, and handfoot syndrome (redness, swelling, and blisters on the palms of the hands and soles of the feet).
Also referred to as rs3918290 or c.1905+1 G>A. The A allele of rs3918290 is associated with toxicity.
Also referred to as c.1679 T>G, I560S or rs55886062
Also referred to as D949V or c.2846A>T
Also referred to as c.1236G>A or E412E; rs56038477