Details

Autor(en) / Beteiligte

• Lanvers-Kaminsky, Claudia
• Sprowl, Jason A
• Malath, Ingrid
• Deuster, Dirk
• Eveslage, Maria
• Schlatter, Eberhard
• Mathijssen, Ron Hj
• Boos, Joachim
• Jürgens, Heribert
• Am Zehnhoff-Dinnesen, Antionette G
• Sparreboom, Alex
• Ciarimboli, Giuliano

Titel

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

Ist Teil von

• Pharmacogenomics, 2015-03, Vol.16 (4), p.323-332

Ort / Verlag

England: Future Medicine Ltd

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

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