Jenny Ortega-Rojas, Carlos E Arboleda-Bustos, Esneyder Guerrero, Juan Neira, Humberto Arboleda
{"title":"哥伦比亚人群中TOMM40、APOE和APOC1基因变异和单倍型与晚发性阿尔茨海默病发病年龄相关","authors":"Jenny Ortega-Rojas, Carlos E Arboleda-Bustos, Esneyder Guerrero, Juan Neira, Humberto Arboleda","doi":"10.1097/WAD.0000000000000477","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The Apolipoprotein E (APOE) gene is the main risk factor for late-onset Alzheimer disease (LOAD). Genetic variants and haplotypes in regions near the APOE locus may be associated with LOAD in the Colombian population.</p><p><strong>Objective: </strong>We evaluated frequencies and risk of genetic variants and haplotypes in APOE, TOMM40, and APOC1 promoters, also in putative regulatory enhancer elements (TOMM40 IVS2-4 and TOMM40 IVS6), and in cis-regulatory elements (ME1 and BCR).</p><p><strong>Materials and methods: </strong>Our case-control association study was carried out in 50 patients with LOAD and 50 controls. We determined frequencies and odd ratios for genetic variants and haplotypes.</p><p><strong>Results: </strong>We found a significant association between LOAD and genetic variants at the TOMM40 promoter, at TOMM40 IVS2-4 and TOMM40 IVS6 regulatory enhancer elements, and at the APOC1 promoter. Particularly, variants of Poly-T and APOC1 promoter could anticipate the age of onset of LOAD in our population. We identified three risk haplotypes in TOMM40 (ACGGAG, ACGGGG, and ATAGGC) related to LOAD's age of onset. We also found other risk or protection haplotypes at the TOMM40 and APOE promoters, at TOMM40 IVS2-4, TOMM40 IVS6 regulatory enhancer elements, and at ME1.</p><p><strong>Conclusion: </strong>Genetic variants and haplotypes near the APOE locus are related to LOAD risk and accelerated onset of LOAD in the Colombian population.</p>","PeriodicalId":520551,"journal":{"name":"Alzheimer disease and associated disorders","volume":" ","pages":"29-35"},"PeriodicalIF":0.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"4","resultStr":"{\"title\":\"Genetic Variants and Haplotypes of TOMM40, APOE, and APOC1 are Related to the Age of Onset of Late-onset Alzheimer Disease in a Colombian Population.\",\"authors\":\"Jenny Ortega-Rojas, Carlos E Arboleda-Bustos, Esneyder Guerrero, Juan Neira, Humberto Arboleda\",\"doi\":\"10.1097/WAD.0000000000000477\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The Apolipoprotein E (APOE) gene is the main risk factor for late-onset Alzheimer disease (LOAD). Genetic variants and haplotypes in regions near the APOE locus may be associated with LOAD in the Colombian population.</p><p><strong>Objective: </strong>We evaluated frequencies and risk of genetic variants and haplotypes in APOE, TOMM40, and APOC1 promoters, also in putative regulatory enhancer elements (TOMM40 IVS2-4 and TOMM40 IVS6), and in cis-regulatory elements (ME1 and BCR).</p><p><strong>Materials and methods: </strong>Our case-control association study was carried out in 50 patients with LOAD and 50 controls. We determined frequencies and odd ratios for genetic variants and haplotypes.</p><p><strong>Results: </strong>We found a significant association between LOAD and genetic variants at the TOMM40 promoter, at TOMM40 IVS2-4 and TOMM40 IVS6 regulatory enhancer elements, and at the APOC1 promoter. Particularly, variants of Poly-T and APOC1 promoter could anticipate the age of onset of LOAD in our population. We identified three risk haplotypes in TOMM40 (ACGGAG, ACGGGG, and ATAGGC) related to LOAD's age of onset. We also found other risk or protection haplotypes at the TOMM40 and APOE promoters, at TOMM40 IVS2-4, TOMM40 IVS6 regulatory enhancer elements, and at ME1.</p><p><strong>Conclusion: </strong>Genetic variants and haplotypes near the APOE locus are related to LOAD risk and accelerated onset of LOAD in the Colombian population.</p>\",\"PeriodicalId\":520551,\"journal\":{\"name\":\"Alzheimer disease and associated disorders\",\"volume\":\" \",\"pages\":\"29-35\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"4\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Alzheimer disease and associated disorders\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1097/WAD.0000000000000477\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Alzheimer disease and associated disorders","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1097/WAD.0000000000000477","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Genetic Variants and Haplotypes of TOMM40, APOE, and APOC1 are Related to the Age of Onset of Late-onset Alzheimer Disease in a Colombian Population.
Background: The Apolipoprotein E (APOE) gene is the main risk factor for late-onset Alzheimer disease (LOAD). Genetic variants and haplotypes in regions near the APOE locus may be associated with LOAD in the Colombian population.
Objective: We evaluated frequencies and risk of genetic variants and haplotypes in APOE, TOMM40, and APOC1 promoters, also in putative regulatory enhancer elements (TOMM40 IVS2-4 and TOMM40 IVS6), and in cis-regulatory elements (ME1 and BCR).
Materials and methods: Our case-control association study was carried out in 50 patients with LOAD and 50 controls. We determined frequencies and odd ratios for genetic variants and haplotypes.
Results: We found a significant association between LOAD and genetic variants at the TOMM40 promoter, at TOMM40 IVS2-4 and TOMM40 IVS6 regulatory enhancer elements, and at the APOC1 promoter. Particularly, variants of Poly-T and APOC1 promoter could anticipate the age of onset of LOAD in our population. We identified three risk haplotypes in TOMM40 (ACGGAG, ACGGGG, and ATAGGC) related to LOAD's age of onset. We also found other risk or protection haplotypes at the TOMM40 and APOE promoters, at TOMM40 IVS2-4, TOMM40 IVS6 regulatory enhancer elements, and at ME1.
Conclusion: Genetic variants and haplotypes near the APOE locus are related to LOAD risk and accelerated onset of LOAD in the Colombian population.
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