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Pharmacogenomics. 2015;16(4):323-32. doi: 10.2217/pgs.14.182.

Human OCT2 variant c.808G>T confers protection effect against cisplatin-induced ototoxicity.

Author information

1
Department of Pediatric Hematology & Oncology, University Children's Hospital of Muenster, Muenster, Germany.

Abstract

AIM:

Assuming that genetic variants of the SLC22A2 and SLC31A1 transporter affect patients' susceptibility to cisplatin-induced ototoxicity, we compared the distribution of 11 SLC22A2 variants and the SLC31A1 variant rs10981694 between patients with and without cisplatin-induced ototoxicity.

PATIENTS & METHODS:

Genotyping was performed in 64 pediatric patients and significant findings were re-evaluated in 66 adults.

RESULTS:

The SLC22A2 polymorphism rs316019 (c.808G>T; Ser270Ala) was significantly associated with protection from cisplatin-induced ototoxicity in the pediatric (p = 0.022) and the adult cohort (p = 0.048; both: Fisher's exact test). This result was confirmed by multiple logistic regression analysis accounting for age which was identified as a relevant factor for ototoxicity as well (rs316019: OR [G/T vs G/G] = 0.12, p = 0.009; age: OR [per year]: 0.84, p = 0.02).

CONCLUSION:

These results identified rs316019 as potential pharmacogenomic marker for cisplatin-induced ototoxicity and point to a critical role of SLC22A2 for cisplatin transport in humans and its contribution to the organ specific side effects of this drug. Original submitted 17 September 2014; Revision submitted 19 December 2014.

KEYWORDS:

SLC22A2; SLC31A1; cisplatin; ototoxicity; polymorphism

PMID:
25823781
PMCID:
PMC4865798
DOI:
10.2217/pgs.14.182
[Indexed for MEDLINE]
Free PMC Article

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