Apolipoprotein E polymorphisms in adults over 60 years of age with mild cognitive impairment and Alzheimer’s disease in different Venezuelan populations

Silvia Martínez , Bárbara Ochoa , María Rafaela Pérez , Fátima Torrico , Ildemaro García , Carmen Cristina Garcia, .

Keywords: Alzheimer’s disease, cognitive dysfunction, dementia, apolipoprotein E4, Venezuela

Abstract

Introduction: Alzheimer’s disease represents a serious public health problem that tends to worsen over time. Among the most important genetic predisposing factors is the presence of the ε4 allele of the apoprotein E gene (APOE).
Objective: To determine the allelic and genotypic frequencies of the APOE isoforms in adults over 60 years old with mild cognitive impairment and Alzheimer’s disease in Gran Caracas and in the indigenous Pemón community of the Kamarata-Kanaimö area, Bolívar State.
Materials and methods: We studied 267 patients: 96 controls, 40 with mild cognitive impairment, 108 with Alzheimer’s from Caracas, and 23 individuals from Kamarata-Kanaimö. The APOE isoforms were determined with the AP1210Z: Seeplex® ApoE Genotyping kit.
Results: The allele ε4 showed a significant association with mild cognitive impairment (OR=5.03; 95% CI: 0.98-25.70) and EA (OR=5.78; 95% CI: 1.24-26.85). The genotype
frequencies for the control and mild cognitive impairment groups were ε3/ε3> ε3/ε4> ε2/ε4> ε3/ε2> ε4/ε4, and for the Alzheimer’s group, ε3/ε3> ε3/ε4> ε4/ε4> ε2/ε4> ε3/ε2 In Kamarata-Kanaimö, the order was ε3/ε3> ε3/ε4> ε4/ε4; the allele ε2 was not found in this group.
Conclusions: APOE allelic and genotypic frequencies in our sample showed a similar distribution to those found in other studies in Venezuela and the Americas. The absence of the ε2 allele in the indigenous community of Kamarata-Kanaimö warrants further investigation. The positive association of the ε4 allele with both Alzheimer’s and mild cognitive impairment was reinforced. The early determination of the ε4 allele carriers can help establish preventive measures in our population.

Downloads

Download data is not yet available.
  • Silvia Martínez Facultad de Farmacia, Universidad Central de Venezuela, Caracas, Venezuela
  • Bárbara Ochoa Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
  • María Rafaela Pérez Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela
  • Fátima Torrico Facultad de Farmacia, Universidad Central de Venezuela, Caracas, Venezuela
  • Ildemaro García Departamento de Cómputo Científico, Universidad Simón Bolívar, Caracas, Venezuela
  • Carmen Cristina Garcia Instituto de Medicina Experimental, Facultad de Medicina, Universidad Central de Venezuela, Caracas, Venezuela

References

World Health Organization. Dementia: A public health priority. Fecha de consulta: 4 de julio de 2017. Disponible en: https://www.who.int/publications/i/item/dementia-a-public-healthpriority

Rodríguez JL, Gutiérrez RF. Demencias y enfermedad de Alzheimer en América Latina y el Caribe. Rev Cubana Salud Pública. 2014;40:378-87.

Fundación Alzheimer de Venezuela. Fecha de consulta: 4 de julio de 2017. Disponible en: https://www.alzheimervenezuela.org

Prince M, Wimo A, Guerchet M, Ali G, Wu Y, Prina M. World Alzheimer’s Report 2015. Fecha de consulta: 10 de agosto de 2017. Disponible en: https://www.alzint.org/resource/worldalzheimer-report-2015/

Instituto Nacional de Estadística. XIV Censo general de población y vivienda. Fecha de consulta: 30 de julio de 2018. Disponible en: http://www.ine.gov.ve/documentos/Demografia/CensodePoblacionyVivienda/pdf/nacional.pdf

Ministerio del Poder Popular para la Salud. Anuarios de mortalidad de Venezuela 2002-2013. Fecha de consulta: 3 de agosto de 2018. Disponible en: https://www.ovsalud.org/publicaciones/documentos-oficiales/

Laws S, Hone E, Gandy S, Martins, R. Expanding the association between the APOE gene and the risk of Alzheimer’s disease: Possible roles for APOE promoter polymorphisms and alterations in APOE transcription. J Neurochem. 2003;84:1215-36. https://doi.org/10.1046/j.1471-4159.2003.01615.x

Rosenberg P, Lyketsos C. Mild cognitive impairment: Searching for the prodrome of Alzheimer’s disease. World Psychiatry. 2008;7:72-8. https://doi.org/10.1002/j.2051-5545.2008.tb00159.x

Farrer L, Cupples L, Haines J, Hyman B, Kukull W, Mayeux R, et al. Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. JAMA. 1997;278:1349-56.

Slooter A, Cruts M, Kalmijn S, Hofman A, Breteler M, van Broeckhoven C, et al. Risk estimates of dementia by apolipoprotein E genotypes from a population-based incidence study: The Rotterdam Study. Arch Neurol. 1998;55:964-8. https://doi.org/10.1001/archneur.55.7.964

Martens R. La ordenación del territorial de Venezuela y su impacto en las comunidades indígenas del municipio Gran Sabana, Edo. Bolívar. Bol Antropol. 2018;36:274-306.

Angosto L. Mundo perdido, paraíso encontrado: lugar, identidad y producción en la Gran Sabana, Venezuela. Rev Colomb Antropol. 2013;49:11-43. https://doi.org/10.22380/2539472X71

Fernández-Mestre M, Castro Y, Montagnani S, Balbas O, Layrisse Z. Genetic variabilitiry of apoliprotein E in different populations from Venezuela. Dis Markers. 2005;21:15-9. https://doi.org/10.1155/2005/625182

Molero A, Pino-Ramírez G, Maestre G. Modulation by age and gender of risk of Alzheimer’s disease and vascular dementia associated with the apolipoprotein E-epsilon 4 allele in Latin Americans: Findings from the Maracaibo Aging Study. Neurosci Lett. 2001;307:5-8. https://doi.org/10.1016/s0304-3940(01)01911-5

Arráiz N, Bermúdez V, Prieto C, Sánchez M, Escalona C, Sanz E, et al. Association between apoliprotein E gene polymorphism and hypercholesterolemic phenotype in Maracaibo, Zulia state, Venezuela. Am J Ther. 2010;17:330-6. https://doi.org/10.1097/MJT.0b013e3181c1235d

Martínez H, Rodríguez-Larralde A, Izaguirre MH, De Guerra DC. Admixture estimates for Caracas, Venezuela, based on autosomal, Y Chromosome, and mtDNA markers. Hum Biol. 2007;79:201-13. https://doi.org/10.1353/hub.2007.0032

Gómez-Carballa A, Veiga A, Álvarez-Iglesias V, Pastoriza-Mourelle A, Ruíz Y, Pineda L, et al. A melting pot of multicontinental mtDNA lineages in admixed Venezuelans. Am J Phys Anthropol. 2012;147:78-87. https://doi.org/10.1002/ajpa.21629

Merriwether DA, Kemp BM, Crews DE, Neel JV. Gene flow and genetic variation in the Yanomami as revealed by mitochondrial DNA. In: Renfrew C, editor. America past, America present: Genes and languages in the Americas and beyond. Cambridge: McDonald Institute for Archaeological Research; 2000. p. 89-124.

Williams SR, Chagnon NA, Spielman RS. Nuclear and mitochondrial genetic variation in the Yanomamo: A test case for ancient DNA studies of prehistoric populations. Am J Phys Anthropol. 2002;117:246-59. https://doi.org/10.1002/ajpa.10035

Bedoya G, Montoya P, García J, Soto I, Bourgeois S, Carvajal L, et al. Admixture dynamics in Hispanics: A shift in the nuclear genetic ancestry of a South American population isolate. Proc Natl Acad Sci USA. 2006;103:7234-9. https://doi.org/10.1073/pnas.0508716103

Carvajal-Carmona L, Ophoff R, Service S, Hartiala J, Molina J, León P, et al. Genetic demography of Antioquia (Colombia) and the Central Valley of Costa Rica. Hum Genet. 2003;112:534-41. https://doi.org/10.1007/s00439-002-0899-8

Mahley R. Central nervous system lipoproteins: ApoE and regulation of cholesterol metabolism. Arterioscler Thromb Vasc Biol. 2016;36:1305-15. https://doi.org/10.1161/ATVBAHA.116.307023

Ruiz M, Arias I, Rolón G, Hernández E, Garavito P, Silvera-Redondo C. Análisis del polimorfismo del gen APOE en la población de Barranquilla, Colombia. Biomédica. 2016;36:52-8. https://doi.org/10.7705/biomedica.v36i1.2612

Arango VJ, Valencia A, Páez A, Montoya N, Palacio C, Arbeláez M, et al. Prevalencia de variantes en el gen de la apoliproteína e (APOE) en adultos de la población general del área urbana de Medellín (Antioquia). Rev Colomb Psiquiatr. 2014;43:80-6. https://doi.org/10.1016/j.rcp.2013.11.012

Marca V, Acosta O, Cornejo M, Ortega O, Huerta D, Mazzetti D. Polimorfismo genético de APOE en una población peruana. Ver Peruana Med Exp Salud Pública. 2011;28:589-94.

Fuzikawa A, Peixoto S, Taufer M, Moriguci E, Lima-Costa M. Apoliprotein E polymorphism distribution in an elderly Brazilian population: The Bambuí health and Aging Study. Braz J Med Biol Res. 2007;40:1429-34. https://doi.org/10.1590/s0100-879x2007001100002

Reiman E, Arboleda-Velásquez J, Quiroz Y, Huentelman M, Beach T, Caselli R, et al. The Alzheimer’s Disease Genetics Consortium. Exceptionally low likelihood of Alzheimer’s dementia in APOE2 homozygotes from a 5,000-person neuropathological study. Nat Commun. 2020;11:667 https://doi.org/10.1038/s41467-019-14279-8

Kim Y, Seo S, Park S, Yang J, Lee J, Lee J, et al. Protective effects of APOE e2 against disease progression in subcortical vascular mild cognitive impairment patients: A three-year longitudinal study. Sci Rep. 2016;7:1910. https://doi.org/10.1038/s41598-017-02046-y

Vívenes M, Garcés MF, Rodríguez G, Lugo F, Celaya J, Rodríguez A. Análisis genético en indígenas Warao del estado Delta Amacuro, Venezuela, en base a las variantes del gen que codifica para la apolipoproteína E. Invest Clin. 2015;56:874-9.

Liu M, Bian C, Zhang J, Wen F. Apolipoprotein E gene polymorphism and Alzheimer’s disease in Chinese population: A meta-analysis. Sci Rep. 2014;4:4383. https://doi.org/10.1038/srep04383

Beydoun M, Boueiz A, Abougergi M, Kitner-Triolo M, Beydoun H, Resnick S, et al. Sex differences in the association of the apolipoprotein E epsilon 4 allele with incidence of dementia, cognitive impairment, and decline. Neurobiol Aging. 2012;33:720-31. https://doi.org/10.1016/j.neurobiolaging.2010.05.017

Altmann A, Tian L, Henderson V, Greicius M. Sex modifies the APOE -related risk of developing Alzheimer disease. Ann Neurol. 2014;75:563-73. https://doi.org/10.1002/ana.24135

Dozzi-Brucki SM, Nitrini R. Cognitive impairment in individuals with low educational level and homogenous sociocultural background. Dement Neuropsychol. 2014;8:345-50. https://doi.org/10.1590/S1980-57642014DN84000007

Caixeta L. Dementia prevalence in an indigenous population from Brazilian Amazon. Alzheimers Dement. 2011:7:S604. https://doi.org/10.1016/j.jalz.2011.05.1715

Moreno DJ, Pino S, Ríos A, Lopera F, Ostos H, et al. Genetic ancestry and susceptibility to late-onset Alzheimer’s Disease (LOAD) in the admixed Colombian population. Alzheimer Dis Assoc Disord. 2017;31:225-31. https://doi.org/10.1097/WAD.0000000000000195

How to Cite
1.
Martínez S, Ochoa B, Pérez MR, Torrico F, García I, Garcia CC. Apolipoprotein E polymorphisms in adults over 60 years of age with mild cognitive impairment and Alzheimer’s disease in different Venezuelan populations. biomedica [Internet]. 2022 May 1 [cited 2024 May 19];42(Sp. 1):116-29. Available from: https://revistabiomedica.org/index.php/biomedica/article/view/5889

Some similar items:

Published
2022-05-01

Altmetric

Article metrics
Abstract views
Galley vies
PDF Views
HTML views
Other views
QR Code