title: Genotype frequencies of drug-metabolizing enzymes responsible for purine and pyrimidine antagonists in a healthy Asian-Indian population.
abstract: Purine and pyrimidine antimetabolites are used to treat leukemias, autoimmune diseases, and solid tumors. Detection of slow metabolizers before administration of the drugs is necessary to prevent any subsequent drug toxicity. With this aim, we determined the frequencies of normal and slow alleles in our population. Polymorphisms in genes encoding cytidine deaminase (CDA), dihydropyrimidine dehydrogenase (DPYD), and thiopurine-S-methyltransferase (TPMT) were documented in 225 healthy volunteers. The polymorphisms typed included CDA*3, DPYD*2A, TPMT*2A, TPMT*3B, and TPMT*3C. Methods used for genotyping included standard PCR-RFLP and allele-specific PCR reactions. The frequencies were 0.44 % for DPYD*2A, 0.67 % for TPMT*3B, and 0.89 % for TPMT*3C. The CDA*3 and TPMT*2A alleles were not detected. Although these polymorphisms have been demonstrated to be associated with drug toxicity in other populations, they appear to be very rare in the adult Indian population.
authors.affiliation: Food Engineering and Technology Department, Institute of Chemical Technology, Matunga, Mumbai 400 019, Maharashtra, India. isandy86@gmail.com
authors.forename: Sandhya N
authors.initials: SN
authors.lastname: Iyer
authors.forename: Ashwini V
authors.initials: AV
authors.lastname: Tilak
authors.forename: Manjari S
authors.initials: MS
authors.lastname: Mukherjee
authors.forename: Rekha S
authors.initials: RS
authors.lastname: Singhal
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D044466:Asian People / Q000235:genetics; D003564:Cytidine Deaminase / Q000235:genetics*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics*; D004789:Enzyme Activation; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population / Q000379:methods; D005838:Genotype; D060005:Genotyping Techniques; D006801:Humans; D007194:India; D008297:Male; D008780:Methyltransferases / Q000235:genetics*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D011687:Purines / Q000037:antagonists & inhibitors*; D011743:Pyrimidines / Q000037:antagonists & inhibitors*; D055815:Young Adult
chemical_list: D011687:Purines; D011743:Pyrimidines; D042943:Dihydrouracil Dehydrogenase (NADP); D008780:Methyltransferases; C022745:thiopurine methyltransferase; D003564:Cytidine Deaminase; C030985:purine