title: Dihydropyrimidine dehydrogenase deficiency in an Indian population.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Yale University School of Medicine, New Haven, CT 06520, USA. wasif.saif@yale.edu
authors.forename: Muhammad Wasif
authors.initials: MW
authors.lastname: Saif
authors.forename: Lori
authors.initials: L
authors.lastname: Mattison
authors.forename: Tom
authors.initials: T
authors.lastname: Carollo
authors.forename: Hany
authors.initials: H
authors.lastname: Ezzeldin
authors.forename: Robert B
authors.initials: RB
authors.lastname: Diasio
mesh_terms: D000328:Adult; D001944:Breath Tests; D002851:Chromatography, High Pressure Liquid; D054067:Dihydropyrimidine Dehydrogenase Deficiency; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics; D017809:Fatal Outcome; D005260:Female; D005838:Genotype; D006801:Humans; D007194:India; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D008297:Male; D008659:Metabolic Diseases / Q000150:complications / Q000175:diagnosis* / Q000201:enzymology; D008875:Middle Aged; D011869:Radioligand Assay; D012680:Sensitivity and Specificity; D013274:Stomach Neoplasms / Q000150:complications / Q000628:therapy
chemical_list: D042943:Dihydrouracil Dehydrogenase (NADP)