Dihydropyrimidine dehydrogenase deficiency in an Indian population

Yale University School of Medicine, New Haven, CT 06520, USA.
Cancer Chemotherapy and Pharmacology (Impact Factor: 2.77). 10/2006; 58(3):396-401. DOI: 10.1007/s00280-005-0174-5
Source: PubMed


Dihydropyrimidine dehydrogenase (DPD) deficiency is prevalent in 3-5% of the Caucasian population; however, the frequency of this pharmacogenetic syndrome in the Indian population and other racial and ethnic groups remains to be elucidated.
We describe an Indian patient who presented to clinic for the treatment of gastric adenocarcinoma with 5-flurouracil (5-FU) therapy who subsequently was diagnosed with DPD deficiency by using the peripheral blood mononuclear cell (PBMC) DPD radioassay. This observation prompted us to examine the data generated from healthy (cancer-free) Indian subjects who were enrolled in a large population study to determine the sensitivity and specificity of the uracil breath test (UraBT) in the detection of DPD deficiency. Thirteen Indian subjects performed the UraBT. UraBT results were confirmed by PBMC DPD radioassay.
The Indian cancer patient demonstrated reduced DPD activity (0.11 nmol/min/mg protein) and severe 5-FU toxicities commonly associated with DPD deficiency. Of the 13 Indian subjects [ten men and three women; mean age, 26 years (range: 21-31 years)] enrolled in the UraBT, 12 Indian subjects demonstrated UraBT breath profiles and PBMC DPD activity within the normal range; one Indian subject demonstrated a reduced breath profile and partial DPD deficiency.
DPD deficiency is a pharmacogenetic syndrome which is also present in the Indian population. If undiagnosed, the DPD deficiency can lead to death. Future epidemiological studies would be helpful to determine the prevalence of DPD deficiency among racial and ethnic groups, allowing for the optimization of 5-FU chemotherapy.

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    • "Dihydropyrimidine dehydrogenase (DPD) is the initial and rate-limiting enzyme in the pathway that catabolizes the pyrimidines such as uracil and thymine [98]. The frequency of low DPD enzyme activity is approximately 3-5% in the general population, but varies significantly among different ethnic populations [99] [100] [101] [102] [103]. DYPD, the gene encoding DPD, is subject to polymorphic variation with over 30 SNPs in the gene described to date, although very few of these SNPs have functional consequences [98]. "
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    • "The frequency of low DPD enzymatic activity in the general population was initially estimated between 3% and 5% [10, 11], although a significant ethnic variability was observed. Indeed, phenotypic and genotypic analyses of Asian [12–15], African [16], European Caucasian [17] and American [18] populations found varying frequencies of DPD deficiency. In particular, African–Americans display significantly lower DPD activity and higher prevalence of DPD deficiency than Caucasians [19], whereas higher value for DPD activity was found in a cohort of Korean subjects. "
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