Pharmacogenetic Study of Deferasirox, an Iron Chelating Agentopen access
- Authors
- Lee, Ji Won; Kang, Hyoung Jin; Choi, Ji-Yeob; Kim, Nam Hee; Jang, Mi Kyung; Yeo, Chang-Woo; Lee, Sang Seop; Kim, Hyery; Park, June Dong; Park, Kyung Duk; Shin, Hee Young; Shin, Jae-Gook; Ahn, Hyo Seop
- Issue Date
- May-2013
- Publisher
- PUBLIC LIBRARY SCIENCE
- Citation
- PLOS ONE, v.8, no.5
- Journal Title
- PLOS ONE
- Volume
- 8
- Number
- 5
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/74856
- DOI
- 10.1371/journal.pone.0064114
- ISSN
- 1932-6203
- Abstract
- Transfusion-associated iron overload induces systemic toxicity. Deferasirox, a convenient long acting oral agent, has recently been introduced in clinical practice with a promising efficacy. But there are some patients who experience drug-related toxicities and cannot tolerate it. To investigate effect of genetic variations on the toxicities and find optimal target population, we analyzed the genetic polymorphisms of UDP-glucuronosyltransferase 1A (UGT1A) subfamily, multi-drug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). A total of 20 functional genetic polymorphisms were analyzed in 98 patients who received deferasirox to reduce transfusion-induced iron overload. We retrospectively reviewed the medical records to find out the drug-related toxicities. Fifteen (15.3%) patients developed hepatotoxicity. Patients without wild-type allele carrying two MRP2 haplotypes containing -1774 del and/or -24T were at increased risk of developing hepatotoxicity compared to patients with the wild-type allele on multivariate analysis (OR = 7.17, 95% CI = 1.79-28.67, P = 0.005). Creatinine elevation was observed in 9 patients (9.2%). Body weight >= 40 kg and homozygosity for UGT1A1*6 were risk factors of creatinine elevation (OR = 8.48, 95% CI = 1.7-43.57, P = 0.010 and OR = 14.17, 95% CI = 1.34-150.35, P = 0.028). Our results indicate that functional genetic variants of enzymes to metabolize and transport deferasirox are associated with drug-related toxicities. Further studies are warranted to confirm the results as the pharmacogenetic biomarkers of deferasirox.
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