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

Claudia Lanvers-Kaminsky1, Jason A Sprowl, Ingrid Malath

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

Pharmacogenomics
|April 1, 2015
PubMed
Abstract

Insights

Genetic variants in the SLC22A2 gene, specifically rs316019, may protect against cisplatin-induced ototoxicity. This finding highlights SLC22A2

Area of Science:

  • Pharmacogenomics
  • Molecular Biology
  • Oncology

Background:

  • Cisplatin is a widely used chemotherapy drug.
  • Ototoxicity is a common and serious side effect of cisplatin treatment.
  • Genetic factors may influence individual susceptibility to cisplatin-induced ototoxicity.

Purpose of the Study:

  • To investigate the association between genetic variants of the SLC22A2 and SLC31A1 transporters and cisplatin-induced ototoxicity.
  • To identify potential pharmacogenomic markers for predicting ototoxicity risk.

Main Methods:

  • Genotyping of 11 SLC22A2 variants and 1 SLC31A1 variant (rs10981694) in pediatric and adult patients.
  • Comparison of variant distribution between patients with and without cisplatin-induced ototoxicity.
  • Statistical analysis including Fisher's exact test and logistic regression.

Main Results:

  • The SLC22A2 polymorphism rs316019 (c.808G>T; Ser270Ala) was significantly associated with protection from cisplatin-induced ototoxicity in both pediatric and adult cohorts.
  • Age was also identified as a significant factor influencing ototoxicity.
  • Logistic regression confirmed the protective effect of rs316019 and the risk associated with age.

Conclusions:

  • The rs316019 variant of SLC22A2 is a potential pharmacogenomic marker for cisplatin-induced ototoxicity.
  • This study underscores the crucial role of SLC22A2 in cisplatin transport and its contribution to ototoxicity.
  • Further research may lead to personalized cisplatin treatment strategies to mitigate ototoxicity.
Keywords:
SLC22A2SLC31A1cisplatinototoxicitypolymorphism

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