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Dissecting the role of Amerindian genetic ancestry and the ApoE ε4 allele on Alzheimer disease in an admixed Peruvian population.
Marca-Ysabel, Maria Victoria; Rajabli, Farid; Cornejo-Olivas, Mario; Whitehead, Patrice G; Hofmann, Natalia K; Illanes Manrique, Maryenela Zaida; Veliz Otani, Diego Martin; Milla Neyra, Ana Karina; Castro Suarez, Sheila; Meza Vega, Maria; Adams, Larry D; Mena, Pedro R; Rosario, Isasi; Cuccaro, Michael L; Vance, Jeffery M; Beecham, Gary W; Custodio, Nilton; Montesinos, Rosa; Mazzetti Soler, Pilar E; Pericak-Vance, Margaret A.
Afiliação
  • Marca-Ysabel MV; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
  • Rajabli F; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Cornejo-Olivas M; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru; Center for Global Health, Universidad Peruana Cayetano Heredia, Lima, Peru.
  • Whitehead PG; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Hofmann NK; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Illanes Manrique MZ; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
  • Veliz Otani DM; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru; Fogarty Northern Pacific Global Health Fellows Program, Lima, Peru; Fogarty Interdisciplinary Cerebrovascular Diseases Training Program in South America, Lima, Peru.
  • Milla Neyra AK; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
  • Castro Suarez S; CBI en Demencias y Enfermedades Desmielinizantes del Sistema Nervioso, Instituto Nacional de Ciencias Neurológicas, Lima, Peru; Atlantic Fellow of Global Brain Health Institute, San Francisco, CA, USA.
  • Meza Vega M; CBI en Demencias y Enfermedades Desmielinizantes del Sistema Nervioso, Instituto Nacional de Ciencias Neurológicas, Lima, Peru; School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru.
  • Adams LD; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Mena PR; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Rosario I; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Cuccaro ML; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Vance JM; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Beecham GW; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA.
  • Custodio N; Instituto Peruano de Neurociencias, Lima, Peru.
  • Montesinos R; Instituto Peruano de Neurociencias, Lima, Peru.
  • Mazzetti Soler PE; Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru; School of Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru.
  • Pericak-Vance MA; John P. Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, FL, USA; Dr. John Macdonald Foundation Department of Human Genetics, University of Miami Miller School of Medicine, Miami, FL, USA. Electronic address: mpericak@med.miami.edu.
Neurobiol Aging ; 101: 298.e11-298.e15, 2021 05.
Article em En | MEDLINE | ID: mdl-33541779
Alzheimer disease (AD) is the leading cause of dementia in the elderly and occurs in all ethnic and racial groups. The apolipoprotein E (ApoE) ε4 is the most significant genetic risk factor for late-onset AD and shows the strongest effect among East Asian populations followed by non-Hispanic white populations and has a relatively lower effect in African descent populations. Admixture analysis in the African American and Puerto Rican populations showed that the variation in ε4 risk is correlated with the genetic ancestral background local to the ApoE gene. Native American populations are substantially underrepresented in AD genetic studies. The Peruvian population with up to ~80 of Amerindian (AI) ancestry provides a unique opportunity to assess the role of AI ancestry in AD. In this study, we assess the effect of the ApoE ε4 allele on AD in the Peruvian population. A total of 79 AD cases and 128 unrelated cognitive healthy controls from Peruvian population were included in the study. Genome-wide genotyping was performed using the Illumina Global screening array v2.0. Global ancestry and local ancestry analyses were assessed. The effect of the ApoE ε4 allele on AD was tested using a logistic regression model by adjusting for age, gender, and population substructure (first 3 principal components). Results showed that the genetic ancestry surrounding the ApoE gene is predominantly AI (60.6%) and the ε4 allele is significantly associated with increased risk of AD in the Peruvian population (odds ratio = 5.02, confidence interval: 2.3-12.5, p-value = 2e-4). Our results showed that the risk for AD from ApoE ε4 in Peruvians is higher than we have observed in non-Hispanic white populations. Given the high admixture of AI ancestry in the Peruvian population, it suggests that the AI genetic ancestry local to the ApoE gene is contributing to a strong risk for AD in ε4 carriers. Our data also support the findings of an interaction between the genetic risk allele ApoE ε4 and the ancestral backgrounds located around the genomic region of ApoE gene.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Indígena Americano ou Nativo do Alasca / Alelos / Apolipoproteína E4 / Estudo de Associação Genômica Ampla / Doença de Alzheimer / Genética Populacional Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male País/Região como assunto: America do sul / Peru Idioma: En Revista: Neurobiol Aging Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Peru País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Indígena Americano ou Nativo do Alasca / Alelos / Apolipoproteína E4 / Estudo de Associação Genômica Ampla / Doença de Alzheimer / Genética Populacional Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Female / Humans / Male País/Região como assunto: America do sul / Peru Idioma: En Revista: Neurobiol Aging Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Peru País de publicação: Estados Unidos