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

C Lanvers-Kaminsky, JA Sprowl, I Malath, D Deuster, M Eveslage, E Schlatter, Ron Mathijssen, J Boos, H Jurgens, AGA Zehnhoff-Dinnesen, A Sparreboom, G Ciarimboli

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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 languageUndefined/Unknown
Pages (from-to)323-332
Number of pages10
JournalPharmacogenomics
Volume16
Issue number4
DOIs
Publication statusPublished - 2015

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