Genotype frequencies of drug-metabolizing enzymes responsible for purine and pyrimidine antagonists in a healthy Asian-Indian population

Biochemical Genetics
Sandhya N IyerRekha S Singhal

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.

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Citations

Nov 5, 2013·International Journal of Biological Macromolecules·Daniela MicozziSilvia Vincenzetti
Sep 3, 2013·Indian Journal of Gastroenterology : Official Journal of the Indian Society of Gastroenterology·Sandeep Kirit DavavalaTarun Gupta
Dec 30, 2014·Indian Journal of Medical and Paediatric Oncology : Official Journal of Indian Society of Medical & Paediatric Oncology·Vijay Gandhi LingaRaghunadharao Digumarti
Aug 15, 2014·Annals of Human Biology·Sandhya N IyerArunkanth Ankala
May 3, 2019·Journal of Gastroenterology and Hepatology·Shintaro AkiyamaTakanori Kanai

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