{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T20:03:39Z","timestamp":1760385819062,"version":"build-2065373602"},"reference-count":39,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T00:00:00Z","timestamp":1608595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["1317_AD-EEGWA","PGC2018-098214-A-I00"],"award-info":[{"award-number":["1317_AD-EEGWA","PGC2018-098214-A-I00"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["POCI-01-0145-FEDER-007274","CEECIND\/00684\/2017","IF\/01262\/2014","CEECIND\/02609\/2017","SFRH\/BPD\/97414\/2013"],"award-info":[{"award-number":["POCI-01-0145-FEDER-007274","CEECIND\/00684\/2017","IF\/01262\/2014","CEECIND\/02609\/2017","SFRH\/BPD\/97414\/2013"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>The primary genetic risk factor for late onset Alzheimer\u2019s disease (LOAD) is the APOE4 allele of Apolipoprotein E (APOE) gene. The three most common variants of APOE are determined by single nucleotide polymorphisms (SNPs) rs429358 and rs7412. Our aim was to estimate allele and genotype frequencies of APOE variants in an Iberian cohort, thus helping to understand differences in APOE-related LOAD risk observed across populations. We analyzed saliva or buccal swab samples from 229 LOAD patients and 89 healthy elderly controls (\u226568 years old) from Northern Portugal and Castile and Le\u00f3n region, Spain. The genotyping was performed by Sanger sequencing, optimized to overcome GC content drawbacks. Results obtained in our Iberian LOAD and control cohorts are in line with previous large meta-analyses on APOE frequencies in Caucasian populations; however, we found differences in allele frequencies between our Portuguese and Spanish subgroups of AD patients. Moreover, when comparing studies from Iberian and other Caucasian cohorts, differences in APOE2 and APOE4 frequencies and subsequent different APOE-related LOAD risks must be clarified. These results show the importance of studying genetic variation at the APOE gene in different populations (including analyses at a regional level) to increase our knowledge about its clinical significance.<\/jats:p>","DOI":"10.3390\/genes12010004","type":"journal-article","created":{"date-parts":[[2020,12,22]],"date-time":"2020-12-22T12:42:28Z","timestamp":1608640948000},"page":"4","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["APOE Variants in an Iberian Alzheimer Cohort Detected through an Optimized Sanger Sequencing Protocol"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1706-6092","authenticated-orcid":false,"given":"Ricardo D.","family":"Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Iva","family":"Gomes","sequence":"additional","affiliation":[{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1194-0941","authenticated-orcid":false,"given":"Catarina","family":"Gomes","sequence":"additional","affiliation":[{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Rita","family":"Rocha","sequence":"additional","affiliation":[{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"given":"Lu\u00eds","family":"Dur\u00e3es","sequence":"additional","affiliation":[{"name":"Associa\u00e7\u00e3o Portuguesa de Familiares e Amigos de Doentes de Alzheimer, 4455-301 Lavra, Portugal"}]},{"given":"Patr\u00edcia","family":"Sousa","sequence":"additional","affiliation":[{"name":"Associa\u00e7\u00e3o Portuguesa de Familiares e Amigos de Doentes de Alzheimer, 4455-301 Lavra, Portugal"}]},{"given":"Manuel","family":"Figueruelo","sequence":"additional","affiliation":[{"name":"Asociaci\u00f3n de Familiares y Amigos de Enfermos de Alzheimer y Otras Demencias de Zamora, 49021 Zamora, Spain"}]},{"given":"Maria","family":"Rodr\u00edguez","sequence":"additional","affiliation":[{"name":"Asociaci\u00f3n de Familiares y Amigos de Enfermos de Alzheimer y Otras Demencias de Zamora, 49021 Zamora, Spain"}]},{"given":"Carmen","family":"Pita","sequence":"additional","affiliation":[{"name":"Asociaci\u00f3n de Familiares y Amigos de Enfermos de Alzheimer y Otras Demencias de Zamora, 49021 Zamora, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9915-2570","authenticated-orcid":false,"given":"Roberto","family":"Hornero","sequence":"additional","affiliation":[{"name":"Grupo de Ingenier\u00eda Biom\u00e9dica, Universidad de Valladolid, 47011 Valladolid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), 47011 Valladolid, Spain"},{"name":"Instituto de Investigaci\u00f3n en Matem\u00e1ticas (IMUVA), Universidad de Valladolid, 47011 Valladolid, Spain"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9488-0605","authenticated-orcid":false,"given":"Carlos","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Grupo de Ingenier\u00eda Biom\u00e9dica, Universidad de Valladolid, 47011 Valladolid, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red en Bioingenier\u00eda, Biomateriales y Nanomedicina (CIBER-BBN), 47011 Valladolid, Spain"}]},{"given":"Alexandra M.","family":"Lopes","sequence":"additional","affiliation":[{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1903-4206","authenticated-orcid":false,"given":"N\u00e1dia","family":"Pinto","sequence":"additional","affiliation":[{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"},{"name":"Centro de Matem\u00e1tica da Universidade do Porto, 4169-007 Porto, Portugal"}]},{"given":"Sandra","family":"Martins","sequence":"additional","affiliation":[{"name":"IPATIMUP\u2013Institute of Molecular Pathology and Immunology of the University of Porto, 4200-135 Porto, Portugal"},{"name":"i3S\u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, 4200-135 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Alzheimer\u2019s Association (2008). 2008 Alzheimer\u2019s disease facts and figures. 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