Human OCT2 variant c.808G>T confers protection effect against cisplatin-induced ototoxicity
| العنوان: | Human OCT2 variant c.808G>T confers protection effect against cisplatin-induced ototoxicity |
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| المؤلفون: | Maria Eveslage, Joachim Boos, Giuliano Ciarimboli, Jason A. Sprowl, Alex Sparreboom, Antionette G am Zehnhoff-Dinnesen, Claudia Lanvers-Kaminsky, Ingrid Malath, Eberhard Schlatter, Heribert Jürgens, Dirk Deuster, Ron H.J. Mathijssen |
| المساهمون: | Medical Oncology |
| المصدر: | Pharmacogenomics, 16(4), 323-332. Future Medicine Ltd. |
| بيانات النشر: | Future Medicine Ltd, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Adult, Male, Oncology, medicine.medical_specialty, Adolescent, Drug-Related Side Effects and Adverse Reactions, Genotype, Organic Cation Transport Proteins, Polymorphism, Single Nucleotide, Article, Ototoxicity, Neoplasms, Internal medicine, Genetics, medicine, Humans, Child, Cation Transport Proteins, Genotyping, Genetic Association Studies, Copper Transporter 1, Pharmacology, Cisplatin, business.industry, Haplotype, Organic Cation Transporter 2, medicine.disease, Exact test, Haplotypes, Child, Preschool, Pharmacogenomics, Cohort, Molecular Medicine, Female, business, medicine.drug |
| الوصف: | 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 |
| تدمد: | 1744-8042 1462-2416 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::18fd35cb51d65ff3c5de5bc0af744749Test https://doi.org/10.2217/pgs.14.182Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....18fd35cb51d65ff3c5de5bc0af744749 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17448042 14622416 |
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