{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T19:09:56Z","timestamp":1789153796482,"version":"build-2803163510"},"reference-count":56,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T00:00:00Z","timestamp":1718668800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"Australian NHMRC Project Grant","doi-asserted-by":"publisher","award":["APP1122387"],"award-info":[{"award-number":["APP1122387"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Dysfunction in ion channels or processes involved in maintaining ionic homeostasis is thought to lower the threshold for cortical spreading depression (CSD), and plays a role in susceptibility to associated neurological disorders, including pathogenesis of a migraine. Rare pathogenic variants in specific ion channels have been implicated in monogenic migraine subtypes. In this study, we further examined the channelopathic nature of a migraine through the analysis of common genetic variants in three selected ion channel or transporter genes: SLC4A4, SLC1A3, and CHRNA4. Using the Agena MassARRAY platform, 28 single-nucleotide polymorphisms (SNPs) across the three candidate genes were genotyped in a case\u2013control cohort comprised of 182 migraine cases and 179 matched controls. Initial results identified significant associations between migraine and rs3776578 (p = 0.04) and rs16903247 (p = 0.05) genotypes within the SLC1A3 gene, which encodes the EAAT1 glutamate transporter. These SNPs were subsequently genotyped in an independent cohort of 258 migraine cases and 290 controls using a high-resolution melt assay, and association testing supported the replication of initial findings\u2014rs3776578 (p = 0.0041) and rs16903247 (p = 0.0127). The polymorphisms are in linkage disequilibrium and localise within a putative intronic enhancer region of SLC1A3. The minor alleles of both SNPs show a protective effect on migraine risk, which may be conferred via influencing the expression of SLC1A3.<\/jats:p>","DOI":"10.3390\/genes15060797","type":"journal-article","created":{"date-parts":[[2024,6,18]],"date-time":"2024-06-18T03:42:06Z","timestamp":1718682126000},"page":"797","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Identification of Polymorphisms in EAAT1 Glutamate Transporter Gene SLC1A3 Associated with Reduced Migraine Risk"],"prefix":"10.3390","volume":"15","author":[{"given":"Cassie L.","family":"Albury","sequence":"first","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8512-1498","authenticated-orcid":false,"given":"Heidi G.","family":"Sutherland","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-6138-1691","authenticated-orcid":false,"given":"Alexis W. Y.","family":"Lam","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngan K.","family":"Tran","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rod A.","family":"Lea","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7735-8110","authenticated-orcid":false,"given":"Larisa M.","family":"Haupt","sequence":"additional","affiliation":[{"name":"Stem Cell and Neurogenesis Group, Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), Kelvin Grove, QLD 4059, Australia"},{"name":"ARC Training Centre for Cell and Tissue Engineering Technologies, Queensland University of Technology(QUT), Kelvin Grove, QLD 4059, Australia"},{"name":"Max Planck Queensland Centre for the Materials Science of Extracellular Matrices, Kelvin Grove, QLD 4059, Australia"},{"name":"Centre for Biomedical Technologies, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6774-5475","authenticated-orcid":false,"given":"Lyn R.","family":"Griffiths","sequence":"additional","affiliation":[{"name":"Genomics Research Centre, Centre for Genomics and Personalised Health, School of Biomedical Sciences, Queensland University of Technology (QUT), 60 Musk Ave., Kelvin Grove, QLD 4059, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,6,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"282","DOI":"10.1016\/j.neurol.2015.01.003","article-title":"Hippocampal modifications in transient global amnesia","volume":"171","author":"Quinette","year":"2015","journal-title":"Rev. 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