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CD33 is a transmembrane receptor that plays an important role in AD pathogenesis by inhibiting amyloid \u03b242 uptake by microglial cells. In this study, we aimed to validate the association between rs3865444 and LOAD risk in the Slovak population and to evaluate whether it was affected by the carrier status of the major LOAD risk allele apolipoprotein (<jats:italic>APOE)<\/jats:italic> \u03b54. <jats:italic>CD33<\/jats:italic> rs3865444 and <jats:italic>APOE<\/jats:italic> variants were genotyped in 206 LOAD patients and 487 control subjects using the polymerase chain reaction\u2013restriction fragment length polymorphism method and direct sequencing, respectively. Logistic regression analysis revealed a significant association of rs3865444 A allele with a reduced LOAD risk that was only present in <jats:italic>APOE<\/jats:italic> \u03b54 allele carriers (AA\u00a0+\u00a0CA versus CC: <jats:italic>p<\/jats:italic>\u00a0=\u00a0.0085; OR\u00a0=\u00a00.45; 95% CI\u00a0=\u00a00.25\u20120.82). On the other hand, no such association was found in subjects without the <jats:italic>APOE<\/jats:italic> \u03b54 (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.75; OR\u00a0=\u00a00.93; 95% CI\u00a0=\u00a00.61\u20121.42). Moreover, regression analysis detected a significant interaction between <jats:italic>CD33<\/jats:italic> rs3865444 A and <jats:italic>APOE<\/jats:italic> \u03b54 alleles (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.021 for <jats:italic>APOE<\/jats:italic> \u03b54 allele dosage and <jats:italic>p<\/jats:italic>\u00a0=\u00a0.051 for <jats:italic>APOE<\/jats:italic> \u03b54 carriage status), with synergy factor (SF) value of 0.49 indicating an antagonistic effect between the two alleles in LOAD risk. In conclusion, our results suggest that <jats:italic>CD33<\/jats:italic> rs3865444:C\u02c3A\u00a0substitution may reduce the risk of LOAD in Slovaks by antagonizing the effect conferred by the major susceptibility allele <jats:italic>APOE<\/jats:italic> \u03b54.<\/jats:p>","DOI":"10.1111\/iji.12489","type":"journal-article","created":{"date-parts":[[2020,4,25]],"date-time":"2020-04-25T05:25:52Z","timestamp":1587792352000},"page":"397-405","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Association of <i>CD33<\/i> rs3865444:C\u02c3A polymorphism with a reduced risk of late\u2010onset Alzheimer's disease in Slovaks is limited to subjects carrying the <i>APOE<\/i> \u03b54 allele"],"prefix":"10.1111","volume":"47","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7741-5779","authenticated-orcid":false,"given":"Juraj","family":"Javor","sequence":"first","affiliation":[{"name":"Institute of Immunology Faculty of Medicine Comenius University in Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladim\u00edra","family":"\u010eurmanov\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Immunology Faculty of Medicine Comenius University in Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuzana","family":"P\u00e1rnick\u00e1","sequence":"additional","affiliation":[{"name":"Institute of Immunology Faculty of Medicine Comenius University in Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Min\u00e1rik","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology Faculty of Natural Sciences Comenius University in Bratislava Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ria","family":"Kr\u00e1lov\u00e1","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Faculty of Medicine Comenius University in Bratislava and University Hospital Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1n","family":"Pe\u010de\u0148\u00e1k","sequence":"additional","affiliation":[{"name":"Department of Psychiatry Faculty of Medicine Comenius University in Bratislava and University Hospital Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbora","family":"Va\u0161e\u010dkov\u00e1","sequence":"additional","affiliation":[{"name":"Psychiatry Outpatient Clinic University Hospital with Polyclinic the Brothers of Saint John of God Bratislava Slovakia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Re\u017en\u00e1kov\u00e1","sequence":"additional","affiliation":[{"name":"Care center Centrum Memory Bratislava 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