Mutational spectrum of dihydropyrimidine dehydrogenase gene (DPYD) in the Tunisian population
- 7 September 2007
- journal article
- research article
- Published by Cellule MathDoc/CEDRAM in Comptes Rendus Biologies
- Vol. 330 (10), 764-769
- https://doi.org/10.1016/j.crvi.2007.08.003
Abstract
Dihydropyrimidine dehydrogenase enzyme (DPD) deficiency is a pharmacogenetic syndrome leading to severe side-effects in patients receiving therapies containing the anticancer drug 5-fluorouracil (5-FU). The aim of this population study is to evaluate gene variations in the coding region of the dihydropyrimidine dehydrogenase gene (DPYD) in the Tunisian population. One hundred and six unrelated healthy Tunisian volunteers were genotyped by denaturing HPLC (DHPLC). Twelve variants in the coding region of the DPYD were detected. Allele frequencies of DPYD*5 (A1627G), DPYD*6 (G2194A), DPYD*9A (T85C), A496G, and G1218A were 12.7%, 7.1%, 13.7%, 5.7%, and 0.5%, respectively. The DPYD alleles DPYD*2A (IVS 14+1g>1), DPYD*3 (1897 del C) and DPYD*4 (G1601A) associated with DPD deficiency were absent from the examined subjects. We describe for the first time a new intronic polymorphism IVS 6-29 g>t, found in an allelic frequency of 4.7% in the Tunisian population. Comparing our data with that obtained in Caucasian, Egyptian, Japanese and African-American populations, we found that the Tunisian population resembles Egyptian and Caucasian populations with regard to their allelic frequencies of DPYD polymorphisms. This study describes for the first time the spectrum of DPYD sequence variations in the Tunisian population.Keywords
This publication has 21 references indexed in Scilit:
- Thymidylate Synthase (TYMS) and Dihydropyrimidine Dehydrogenase (DPYD) Polymorphisms in the Korean Population for Prediction of 5-Fluorouracil-Associated ToxicityTherapeutic Drug Monitoring, 2007
- Analysis of the DPYD Gene Implicated in 5-Fluorouracil Catabolism in a Cohort of Caucasian IndividualsClinical Cancer Research, 2005
- Detailed analysis of five mutations in dihydropyrimidine dehydrogenase detected in cancer patients with 5-fluorouracil-related side effectsHuman Mutation, 2003
- Use of Pyrosequencing to Detect Clinically Relevant Polymorphisms in Dihydropyrimidine DehydrogenaseClinical Chemistry, 2003
- Allele and genotype frequencies of polymorphic cytochromes P450 (CYP2C9, CYP2C19, CYP2E1) and dihydropyrimidine dehydrogenase (DPYD) in the Egyptian populationBritish Journal of Clinical Pharmacology, 2002
- Dihydropyrimidine dehydrogenase pharmacogenetics in Caucasian subjectsBritish Journal of Clinical Pharmacology, 1998
- Characterization of the Human Dihydropyrimidine Dehydrogenase GeneGenomics, 1998
- Diagnostic analysis, clinical importance and molecular basis of dihydropyrimidine dehydrogenase deficiencyTrends in Pharmacological Sciences, 1995
- Human Polymorphism in Drug Metabolism: Mutation in the Dihydropyrimidine Dehydrogenase Gene Results in Exon Skipping and Thymine UracilureaDNA and Cell Biology, 1995
- Assignment of the Human Dihydropyrimidine Dehydrogenase Gene (DPYD) to Chromosome Region 1p22 by Fluorescence in Situ HybridizationGenomics, 1994