Scientific background: |
DPYD(Dihydropyrimidine Dehydrogenase), also called DPD, is an enzyme that in humans is encoded
by the DPYD gene. The protein encoded by this gene is a pyrimidine catabolic enzyme and the initial
and rate-limiting factor in the pathway of uracil and thymidine catabolism. The structure of
the DPYD gene contains 23 exons spanning about 950 kb. Using somatic cell hybrid
strategies, the DPYD gene is mapped to the centromeric region of chromosome 1 between 1p22 and
1q21. By fluorescence in situ hybridization, the DPYD gene is mapped to 1p22. The highest level of
DPD was found in monocytes followed by that in lymphocytes, granulocytes, and platelets, whereas no
significant activity of DPD could be detected in erythrocytes. The activity of DPD in peripheral blood
mononuclear cells was intermediate between that observed in monocytes and lymphocytes. By cDNA
microarray, Western blot analysis, and luciferase reporter assay, the transcription factor LSF was
identified as a positive regulator of DPYD. |
References: |
Albin, N., Johnson, M. R., Shahinian, H., Wang, K., Diasio, R. B. Initial characterization of the
molecular defect in human dihydropyrimidine dehydrogenase deficiency. Proc. Am. Assoc. Cancer
Res. (Abstract) 36: 211 only, 1995.
2. McLeod, H. L., Collie-Duguid, E. S. R., Vreken, P., Johnson, M. R., Wei, X., Sapone, A., Diasio, R.
B., Fernandez-Salguero, P., van Kuilenberg, A. B. P., van Gennip, A. H., Gonzales, F.
J. Nomenclature for human DPYD alleles. Pharmacogenetics 8: 455-459, 1998.
3. Ridge, S. A., Brown, O., McMurrough, J., Fernandez-Salguero, P., Evans, W. E., Gonzalez, F. J.,
McLeod, H. L. Mutations at codon 974 of theDPYD gene are a rare event. Brit. J. Cancer 75:
178-179, 1997. |