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- Title
Pharmacogenetic Study of Deferasirox, an Iron Chelating Agent
- 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
- 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.
- Subjects
PHARMACOGENOMICS; CHELATING agents; DEFERASIROX; GLUCURONOSYLTRANSFERASE; GENETIC polymorphisms; ORAL drug administration; DRUG toxicity
- Publication
PLoS ONE, 2013, Vol 8, Issue 5, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0064114