The Dihydropyrimidine dehydrogenase DPYD gene encodes the enzyme of that same name, a pyrimidine catabolic enzyme and the initial and rate-limiting factor in the pathway of uracil and thymidine catabolism. SNPs leading to deficiency of this enzyme result in an error in pyrimidine metabolism associated with thymine-uraciluria and an increased risk of toxicity in cancer patients undergoing chemotherapy using fluoropyrimidines such as 5-fluorouracil. Wikipedia
Mutations in the DPYD gene that result in a nonfunctional allele and therefore influence chemotherapeutic toxicity include:
- rs55886062(C), the DPYD*13 allele
- rs3918290(A), DPYD*2A
- rs67376798(A), as defined on the plus strand
Carriers of one nonfunctional allele are considered intermediate metabolizers; carriers of two nonfunctional alleles are poor metabolizers. These diplotypes are tested by genosets gs313, gs312 and gs306, representing the predicted presence of 0, 1 or 2 nonfunctional alleles, respectively.