KCNK17 genetic variants in ischemic stroke

Sophie Domingues-Montanari, Israel Fernández-Cadenas, Alberto del Río-Espinola, Maite Mendioroz, Jessica Fernandez-Morales, Natalia Corbeto, Pilar Delgado, Marc Ribó, Marta Rubiera, Victor Obach, Joan Martí-Fàbregas, Marimar Freijo, Joaquin Serena, Joan Montaner

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    Abstract

    Background: Genetic factors contribute to the development of ischemic stroke (IS). In order to identify susceptibility variants, we analyzed single nucleotide polymorphisms (SNPs) that had been previously linked to stroke in a genome-wide association study. Methods: We analyzed 12 SNPs in a White population comprising IS patients and healthy controls. The analysis was adjusted for confounding variables and stratified by stroke etiology. Functional studies were then performed to elucidate the role of these variants in IS. Results: In a preliminary analysis of 268 controls and 531 IS cases, the rs10947803 SNP of KCNK17 (p = 0.012) and the rs7506045 of IMPA2 (p = 0.040) were associated with IS, although only the KCNK17 gene was an independent risk factor for IS. In a second phase, analysis of 271 new IS cases revealed that the A allele of rs10947803 was associated with stroke after correction for Bonferroni (OR = 1.48; 95% CI, 1.14-1.91, p = 0.003). Gene expression analysis revealed that KCNK17 mRNA levels were higher in the IS cases in the acute phase than in controls (14 ± 78% vs. 91 ± 41, p = 0.002) but not in the chronic phase (56 ± 57%; p = 0.230). Moreover, RNA levels depended on the alleles of the rs10947803 SNP in the control group (p = 0.021) and in the chronic phase (p = 0.033). Conclusions: The A allele of the rs10947803 variant of KCNK17 was associated with increased risk of IS and increased levels of KCNK17 gene expression. The role of this potassium channel gene in IS opens diagnostic and therapeutic expectations and merits further investigation. © 2009 Elsevier Ireland Ltd. All rights reserved.
    Original languageEnglish
    Pages (from-to)203-209
    JournalAtherosclerosis
    Volume208
    Issue number1
    DOIs
    Publication statusPublished - 1 Jan 2010

    Keywords

    • Genetics
    • Ischemic stroke
    • KCNK17
    • TALK
    • TASK

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    Domingues-Montanari, S., Fernández-Cadenas, I., del Río-Espinola, A., Mendioroz, M., Fernandez-Morales, J., Corbeto, N., Delgado, P., Ribó, M., Rubiera, M., Obach, V., Martí-Fàbregas, J., Freijo, M., Serena, J., & Montaner, J. (2010). KCNK17 genetic variants in ischemic stroke. Atherosclerosis, 208(1), 203-209. https://doi.org/10.1016/j.atherosclerosis.2009.07.023