title: Determination of common genetic variants in cytidine deaminase (CDA) gene in Indian ethnic population.
abstract: Cytidine deaminase (CDA) is the major enzyme involved in metabolism of gemcitabine, a pyrimidine analog widely used for chemotherapy of solid tumors. While only low amounts of administered gemcitabine undergo intracellular phosphorylation into active forms and involve in antineoplastic activities, majority of it is rapidly inactivated by CDA and excreted to avoid drug toxicity. Knowledge of the genetic polymorphisms mildly effecting cellular activity of the enzyme CDA is therefore crucial to understanding drug-induced toxicities associated with gemcitabine. Functional significance and allele frequencies for common SNPs including 79A>C (*2) and 208G>A (*3) have been reported in various ethnic populations including Caucasian, African, Korean and Japanese. However, such studies have not been reported in any Indian sub-population. In the present study, conventional polymerase chain reaction (PCR) based amplification using gene specific primers and Sanger sequencing were performed to identify CDA variants in 50 healthy individuals from Indian sub-population. Established common variant 79A>C known to reduce CDA activity was observed at a frequency of 0.14 in the study cohort. In addition to other known variants, one novel variant, c.325-209T>C was detected at a frequency of 0.06. Genetic variants in CDA gene and their frequencies established in our study hold value in pharmacogenetics.
authors.affiliation: Food Engineering and Technology Department, Institute of Chemical Technology, Matunga, Mumbai-400019, India. isandy86@gmail.com
authors.forename: Sandhya N
authors.initials: SN
authors.lastname: Iyer
authors.forename: Arunkanth
authors.initials: A
authors.lastname: Ankala
authors.forename: Rekha S
authors.initials: RS
authors.lastname: Singhal
authors.forename: Madhuri R
authors.initials: MR
authors.lastname: Hegde
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D015331:Cohort Studies; D003564:Cytidine Deaminase / Q000235:genetics*; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D005819:Genetic Markers; D005828:Genetics, Population; D006801:Humans; D007194:India; D007438:Introns; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics; D010865:Pilot Projects; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide
chemical_list: D005819:Genetic Markers; D003564:Cytidine Deaminase