Possible association of CAG repeat polymorphism in KCNN3 encoding the potassium channel SK3 with oxaliplatin-induced neurotoxicity

Cancer Chemotherapy and Pharmacology
Benjamin AnonThierry Lecomte

Abstract

Data suggest a role of the potassium channel SK3 (KCNN3 gene) in oxaliplatin-induced neurotoxicity (OIN). Length variations in the polymorphic CAG repeat of the KCNN3 gene may be associated with the risk of OIN. We performed patch-clamp experiments on HEK293 cell lines, expressing SK3 channel isoforms with short (11) or long (24) CAG repetitions, to measure intracellular calcium concentrations to test the effects of oxaliplatin on current density. A retrospective study was carried out on patients with colorectal cancer who had received oxaliplatin-based chemotherapy. DNA for KCNN3 genotyping was extracted from leukocytes. The region containing the CAG repeats was amplified by PCR and the products separated by capillary electrophoresis for length analysis. The patients were divided into three groups depending on whether they carried two short alleles, one short allele and one long allele, or two long alleles. The primary endpoint was the onset of grade 2 or 3 neuropathy to oxaliplatin. There was no difference in current density, but oxaliplatin induced a differential effect on apamin-sensitive current density between the two isoforms expressed in the HEK cell lines. There was a significant reduction of store-operated calcium ent...Continue Reading

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Citations

Nov 7, 2019·Journal of the Peripheral Nervous System : JPNS·Anna Modoni, Michele Basso
Sep 6, 2019·Journal of the Peripheral Nervous System : JPNS·Andreas A ArgyriouHaralabos P Kalofonos
Aug 7, 2021·Journal of Personalized Medicine·Roser VelascoAndreas A Argyriou

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