Journal
PHARMACOGENOMICS
Volume 12, Issue 4, Pages 503-514Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/PGS.10.200
Keywords
cytarabine; cytidine deaminase; hematotoxicity; pharmacogenomics
Categories
Funding
- German Jose Carreras Leukemia foundation e.V [DJCI S R08/11]
Ask authors/readers for more resources
Aim: To adopt an individualized approach to assess cytarabine (ara-C) hematotoxicity, we studied the relationship between pharmacogenetic variability in the cytidine deaminase gene (CDA) and ara-C toxicity in native peripheral blood mononuclear cells from 100 healthy volunteers. Materials & methods: Peripheral blood mononuclear cells were incubated for 48 h with 3 mu M ara-C, and cell viability was analyzed by flow cytometry with and without the addition of an equilibrative nucleoside transporter transport inhibitor. CDA promoter and exonic variants were genotyped to derive haplotypes for the CDA gene. Results: Significant between-subject variability was observed in ara-C toxicity (21-fold with 40.1% coefficient of variation compared with 1.2-fold within-subject variability [9.6% coefficient of variation]). Inhibition of hENT1 reversed ara-C cytotoxicity. The linked CDA promoter variants -451C>T, -92A>G, -31Del and the exonic 79A>C variant were associated with ara-C toxicity (p < 0.05). CDA*2A haplotype was associated with ara-C toxicity (p = 0.03). Conclusion: Genetic polymorphisms within CDA may be risk factors for ara-C-induced hematotoxicity.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available