Human OCT2 variant c.808G>T confers protection effect against cisplatin-induced ototoxicity.
Pharmacogenomics
; 16(4): 323-32, 2015.
Article
en En
| MEDLINE
| ID: mdl-25823781
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.Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Cisplatino
/
Proteínas de Transporte de Catión
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Proteínas de Transporte de Catión Orgánico
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Neoplasias
Tipo de estudio:
Prognostic_studies
Límite:
Adolescent
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Adult
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Child
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Child, preschool
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Female
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Humans
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Male
Idioma:
En
Año:
2015
Tipo del documento:
Article