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Title: KATP channel expression and genetic polymorphisms associated with progression and survival in amyotrophic lateral sclerosis.
Author: Vidal Taboada, José Manuel
Pugliese, Marco
Salvado, Maria
Gamez, Josep
Mahy Gehenne, Josette Nicole
Rodríguez Allué, Manuel José
Keywords: Esclerosi lateral amiotròfica
Teràpia genètica
Canals de potassi
Amyotrophic lateral sclerosis
Gene therapy
Potassium channels
Issue Date: Oct-2018
Publisher: Humana Press.
Abstract: The ATP-sensitive potassium (KATP) channel directly regulates the microglia-mediated inflammatory response following CNS injury. To determine the putative role of the KATP channel in amyotrophic lateral sclerosis (ALS) pathology, we investigated whether ALS induces changes in KATP channel expression in the spinal cord and motor cortex. We also characterized new functional variants of human ABCC8, ABCC9, KCNJ8, and KCNJ11 genes encoding for the KATP channel and analyzed their association with ALS risk, rate of progression, and survival in a Spanish ALS cohort. The expression of ABCC8 and KCNJ8 genes was enhanced in the spinal cord of ALS samples, and KCNJ11 increased in motor cortex of ALS samples, as determined by real-time polymerase chain reaction. We then sequenced the exons and regulatory regions of KATP channel genes from a subset of 28 ALS patients and identified 50 new genetic variants. For the case-control association analysis, we genotyped five selected polymorphisms with predicted functional relevance in 185 Spanish ALS (134 spinal ALS and 51 bulbar ALS) patients and 493 controls. We found that bulbar ALS patients presenting the G/G genotype of the rs4148646 variant of ABCC8 and the T/T genotype of the rs5219 variant of KCNJ11 survived longer than other ALS patients presenting other genotypes. Also, the C/C genotype of the rs4148642 variant of ABCC8 and the T/C genotype of the rs148416760 variant of ABCC9 modified the progression rate in spinal ALS patients. Our results suggest that the KATP channel plays a role in the pathophysiological mechanisms of ALS.
Note: Versió postprint del document publicat a:
It is part of: Molecular Neurobiology, 2018, vol. 55, num. 10, p. 7962-7972
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ISSN: 0893-7648
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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