title: Mutational spectrum of dihydropyrimidine dehydrogenase gene (DPYD) in the Tunisian population.
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.
authors: Metabolic Biophysics and Applied Pharmacology Laboratory, Department of Biophysics, Medicine Faculty of Sousse, 4002 Sousse, Tunisia. radhyouna@yahoo.fr
authors: Radhia
authors: R
authors: Ben Fredj
authors: Eva
authors: E
authors: Gross
authors: Lotfi
authors: L
authors: Chouchen
authors: Fatma
authors: F
authors: B'Chir
authors: Slim
authors: S
authors: Ben Ahmed
authors: Steffi
authors: S
authors: Neubauer
authors: Marion
authors: M
authors: Kiechle
authors: Saâd
authors: S
authors: Saguem
mesh_terms: D000328:Adult; D000368:Aged; D018912:Arabs / Q000235:genetics*; D004252:DNA Mutational Analysis; D054067:Dihydropyrimidine Dehydrogenase Deficiency / Q000453:epidemiology / Q000208:ethnology / Q000235:genetics*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D014416:Tunisia / Q000453:epidemiology
chemical_list: D042943:Dihydrouracil Dehydrogenase (NADP)