Genotypic and allelic frequencies of apolipoprotein e (APOE) in a sample of adults in bogotá

Frecuencias genotípicas y alélicas de apolipoproteina e (APOE) en una muestra de adultos en Bogotá

Main Article Content

Cladelis Rubio Gómez
Luz Dary Gutiérrez Castañeda
Olga Lucia Pedraza
Lilian Torres Tobar
Gualberto Hernández Acevedo
Alfonso Suárez Camacho
Ángela Gisselle Lozano Ruiz
Isis Norella Camacho-Bermúdez

Abstract

Introduction: apolipoprotein E (APOE) is a glycoprotein involved in the transport of lipid molecules. Three alleles of the APOE gene have been described: Ɛ2, Ɛ3 and Ɛ4. Several studies show an association of the APOE isoform with late-onset Alzheimer´s disease. Objectives: to determine the genotypic and allelic frequencies of the APOE gene in an adult sample in Bogotá. Materials and Methods: a cross-sectional observational descriptive study. Genomic DNA was extracted from a peripheral blood sample and APOE alleles and genotypes were determined using the PCR tetra-primer method. Results: we included 1254 subjects, 942 women (75%) and 312 men (25%) aged between 40 and 100 years. The most frequent allele was Ɛ3 (85%), followed by Ɛ4 (11%) and Ɛ2 (2%). Of the population that declared to have Cundinamarca and Boyacá sub-regions ancestry, 567 subjects (74.6%) had genotype Ɛ3/Ɛ3, while 156 (20.4%) had Ɛ3/Ɛ4, 23 (3%) Ɛ2/Ɛ3, 11 (1.5%) Ɛ4/Ɛ4 and 4 (0.5%) had genotype Ɛ2/Ɛ4. The individuals with genotype Ɛ2/Ɛ2 declared not to know the data on their ancestry. Conclusions: the allelic and genotypic frequencies of APOE vary according to ethnic origin. However identifying subjects with the less frequent genotype (Ɛ2/Ɛ2) is possible when analyzing larger samples. In previous reports in the country, genotype Ɛ2/Ɛ2, has not been described and was identified in the present sample as the one with the lowest proportion.

Keywords:

Downloads

Download data is not yet available.

Article Details

References

MedlinePlus Connect for EHRs. APOE gene, apolipoprotein E [Internet]. MedlinePlus; 2020 [cited 2019 septiembre 14]; Available from: https://medlineplus.gov/genetics/gene/apoe/.

Mahley RW, Weisgraber KH, Huang Y. Apolipoprotein E4: a causative factor and therapeutic target in neuropathology, including Alzheimer's disease. Proc Natl Acad Sci. 2006;103(15):5644-51. doi: 10.1073/pnas.0600549103

Rall SC Jr, Weisgraber KH, Innerarity TL, Mahley RW Structural basis for receptor binding heterogeneity of Apolipoprotein E from type III hyperlipoproteinemic subjects. Proc Natl Acad Sci U S A. 1982;79(15):4696-700. doi: 10.1073/pnas.79.15.4696

Wilson C, Wardell MR, Weisgraber KH, Mahley RW, Agard DA. Three-dimensional structure of the LDL receptor-binding doamin of human apolipoprotein E. Science. 1991;252(5014):1817-22. doi: 10.1126/science.2063194

Hixson JE, Vernier DT. Restriction isotyping of human apolipoprotein E by gene amplification and cleavage with HhaI. J Lipid Res. 1990;31:545-8.

Weisgraber KH, Rall SC, Jr., Mahley RW. Human E apoprotein heterogeneity. Cysteine-arginine interchanges in the amino acid sequence of the apo-E isoforms. J BiolChem. 1981;256 (17):9077-83. doi: 10.1016/s0021-9258(19)52510-8

Davignon J, Gregg RE, Sing CF. Apolipoprotein E polymorphism and atherosclerosis. Arteriosclerosis. 1988; (1):1-21. doi: 10.1161/01.atv.8.1.1

Huebbe P, Rimbach G. Evolution of human apolipoprotein E (APOE) isoforms: Gene structure, protein function and interaction with dietary factors. Ageing Res Rev. 2017;37:146-61. doi: 10.1016/j.arr.2017.06.002

Singh PP, Singh M, Mastana SS. APOE distribution in world populations with new data from India and the UK. Ann Hum Biol. 2006;33(3):279-308. doi: 10.1080/03014460600594513

Gerdes LU, Gerdes C., Hansen PS, Klausen IC., Faergeman, O., Dyerberg J. The apolipoprotein E polymorphism in Greenland Inuit in its global perspective. Hum Genet. 1996;98(5):546-50. doi: 10.1007/s004390050257

Mastana SS, Calderon R, Pena J, Reddy PH, & Papiha SS. Anthropology of the apolipoprotein E (apo E) gene: Low frequency of apo E4 allele in Basques and in tribal (Baiga) populations of India. Ann Hum Biol. 1998;25(2):137-43. doi: 10.1080/03014469800005512

Corbo RM, & Scacchi, R. Apolipoprotein E (APOE) allele distribution in the world. Is APOE* 4 a ‘thrifty’allele? Ann Hum Genet. 1999;63(4):301-10. doi: 10.1046/j.1469-1809.1999.6340301.x

Singh P, Singh M, Gerdes U, Mastana SS. Apolipoprotein E polymorphism in India: high APOE* E3 allele frequency in Ramgarhia of Punjab. Anthropol Anz. 2001;59(1):27-34.

Singh PP, Singh M, Mastana SS. Genetic variation of apolipoproteins in North Indians. Hum Biol. 2002;74(5):673-82. doi: 10.1353/hub.2002.0057

Martínez‐Oliván J, Arias‐Moreno X, Velazquez‐Campoy A, Millet O, Sancho J. LDL receptor/lipoprotein recognition: endosomal weakening of ApoB and ApoE binding to the convex face of the LR5 repeat. FEBS J. 2014;281(6):1534-46. doi: 10.1111/febs.12721

Corder EH, Saunders AM, Strittmatter WJ, Schmechel DE, Gaskell PC, Small GW,Roses AD, Haines JL, Pericak-Vance MA. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science. 1993;261(5123):921-3. doi: 10.1126/science.8346443

Fei M, Jianhua W. Apolipoprotein epsilon4-allele as a significant risk factor for conversion from mild cognitive impairment to Alzheimer’s disease: a meta-analysis of prospective studies. J Mol Neurosci. 2013;50:257-63. doi: 10.1007/s12031-012-9934-y

Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD. Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA. 1993;90(5):1977-81. doi: 10.1073/pnas.90.5.1977

Coon KD, Myers AJ, Craig DW, Webster JA ,Pearson JV, Lince DH et al. A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer's disease. J Clin Psychiatry. 2007;68(4):613-8. doi: 10.4088/jcp.v68n0419

Sureshkumar R, Bharath S, Jain S, Prakash O, Purushottam M, Thennarasu K, et al. ApoE4 and late onset depression in Indian population. J Affect Disord. 2012;136(3):244-248. doi: 10.1016/j.jad.2011.12.022

Lavretsky H, Ercoli L, Siddarth P, Bookheimer S, Miller K, Small G. Apolipoprotein epsilon4 allele status, depressive symptoms, and cognitive decline in middle-aged and elderly persons without dementia. Am J Geriatr Psychiatry. 2003;11(6):667-673. doi: 10.1176/appi.ajgp.11.6.667

Soeira-de-Souza MG, Bio DS, Dias VV, Martins do Prado C, Campos RN, Costa LF, et al. Apolipoprotein E genotype and cognition in bipolar disorder. CNS Neurosci Ther. 2010;16(5):316-321. doi: 10.1111/j.1755-5949.2010.00153.x

Bellivier F, Laplanche JL, Schurhoff F, Feingold J, Feline A, Jouvent R, et al. Apolipoprotein E gene polymorphism in early and late onset bipolar patients. Neurosci Lett. 1997;223(1):45-48. doi: 10.1016/s0304-3940(97)00624-1

Corder EH, Saunders AM, Risch NJ, Strittmatter WJ, Schmechel DE, Gaskell Jr PC, et al. Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nat Genet. 1994;7(2):180-4. doi: 10.1038/ng0694-180

Genin E, Hannequin D, Wallon D, Sleegers K, Hiltunen M, Combarros O, et al. APOE and Alzheimer disease: a major gene with semi-dominant inheritance. Mol Psychiatry. 2011;16(9):903-7. doi: 10.1038/mp.2011.52

Rojas W, Parra MV, Campo O, Caro MA, Lopera JG, Arias W et al. Genetic make up and structure of Colombian populations by means of uniparental and biparental DNA markers. Am J Phys Anthropol. 2010;143(1):13-20. doi: 10.1002/ajpa.21270

Arango Viana JC VA, Páez AL, Montoya Gómez N, Palacio C, Arbeláez MP, Bedoya Berrío G, García Valencia J. Prevalence of Variants in the Apolipoprotein E (APOE) Gene in a General Population of Adults from an Urban Area of Medellin (Antioquia). Rev Colomb Psiquiatr. 2014;43(2):80-6. doi: 10.1016/j.rcp.2013.11.012

Jacquier M, Arango D, Villareal E, Torres O, Serrano ML, Cruts M et al. APOE epsilon4 and Alzheimer's disease: positive association in a Colombian clinical series and review of the Latin-American studies. Arq Neuropsiquiatr. 2001;59(1):11-7. doi: 10.1590/s0004-282x2001000100004

Forero DA, Pinzón J, Arboleda GH, Yunis JJ, Alvarez C, Cataño et al. Analysis of common polymorphisms in angiotensin-converting enzyme and apolipoprotein E genes and human longevity in Colombia. Arch Med Res. 2006;37(7):890-4. doi: 10.1016/j.arcmed.2006.04.001

Velez-Pardo C, Rojas W, Jimenez-Del-Rio M, Bedoya G. (2014). Distribution of APOE polymorphism in the “Paisa” population from northwest Colombia (Antioquia). Ann Hum Biol 2014;42(2):195-8. doi: 10.3109/03014460.2014.932846

Landázuri P, Loango, N., Gallego, M. L., & Restrepo, B. Diferencias de sexo, edad y lípidos plasmáticos asociadas al polimorfismo de la apolipoproteína E en un grupo de escolares de Quindío, Colombia. Biomédica. 2009;29(3):382-91. doi: 10.7705/biomedica.v29i3.10

Ruiz M, Arias, I., Rolon, G., Hernández, E., Garavito, P., & Silvera-Redondo, C. A. Análisis del polimorfismo del gen APOE en la población de Barranquilla, Colombia. Biomédica. 2015;36(1):52-58. doi: 10.7705/biomedica.v36i1.2612

Jaramillo-Correa JP, Keyeux, G., Ruiz-Garcia, M., Rodas, C., & Bernal, J. Population genetic analysis of the genes APOE, APOB (3′ VNTR) and ACE in some black and Amerindian communities from Colombia. Human Hered. 2001;52(1):14-33. doi: 10.1159/000053351

Pedraza OL, Salazar AM, Sierra FA, Montalvo C, Muñoz Y, Díaz JM, et al. Mild cognitive impairment (MCI) and dementia in a sample of adults in the city of Bogotá. Dement Neuropsychol 2017;11(3):262-26. doi: 10.1590/1980-57642016dn11-030008

Yang YG KJ, Park SJ, Kim SW, Jeon O, Kim D. Apolipoprotein E genotyping by multiplex tetra-primer amplification refractory mutation system PCR in single reaction tube. J Biotechnol. 2007;131(2):106-10. doi: 10.1016/j.jbiotec.2007.06.001

Bertram L, & Tanzi, R. E. Genome-wide association studies in Alzheimer's disease. Human molecular genetics. 2009;18(R2): R137-45. doi: 10.1093/hmg/ddp406

Caselli RJ, Dueck, A. C., Osborne, D., Sabbagh, M. N., Connor, D. J., Ahern, G. L., Baxter, L. C., Rapcsak, S. Z., Shi, J., Woodruff, B. K., Locke, D. E. C., Snyder, C. H., Alexander, G. E., Rademakers, R., Reiman, E. M. Longitudinal modeling of age-related memory decline and the APOE epsilon-4 effect. New Eng J Med. 2009;361(3):255-63. doi: 10.1056/NEJMoa0809437

Baxter LC CR, Johnson SC, Reiman E, Osborne D. Apolipoprotein E epsilon 4 affects new learning in cognitively normal individuals at risk for Alzheimer’s disease. Neurobiol Aging. 2003;24(7):947-52. doi: 10.1016/s0197-4580(03)00006-x

Caselli RJ RE, Osborne D, et al. Longitudinal changes in cognition and behavior in asymptomatic carriers of the APOE e4 allele. Neurology. 2004;62(11): 1990-5. doi: 10.1212/01.wnl.0000129533.26544.bf

Caselli RJ RE, Locke DE, et al. Cognitive domain decline in healthy apolipoprotein E epsilon4 homozygotes before the diagnosis of mild cognitive impairment. Arch Neurol. 2007;64(9):1306-1311.

Reiman EM, Caselli, R. J., Chen, K., Alexander, G. E., Bandy, D., Frost, J. Declining brain activity in cognitively normal apolipoprotein E epsilon-4 heterozygotes: a foundation for using positron emission tomography to efficiently test treatments to prevent Alzheimer's disease. Proc Nat Acad Sci USA. 2001;98(6):3334-9. doi: 10.1073/pnas.061509598

Reiman EM, Caselli, R. J., Yun, L. S., Chen, K., Bandy, D., Minoshima, S., Thibodeau, S. N., Osborne, D. Preclinical evidence of Alzheimer's disease in persons homozygous for the epsilon-4 allele for apolipoprotein E. New Eng J Med. 1996;334(12):752-8. doi: 10.1056/NEJM199603213341202

Reiman EM, Chen, K., Alexander, G. E., Caselli, R. J., Bandy, D., Osborne, D., Saunders, A. M., Hardy, J. Functional brain abnormalities in young adults at genetic risk for late-onset Alzheimer's dementia. Proc Nat Acad Sci. 2004;101(1):284-9. doi: 10.1073/pnas.2635903100

Marca V AO, Cornejo-Olivas M, Ortega O, Huerta D, Mazzetti P. Genetic polymorphism of apolipoprotein E in a Peruvian population. Rev Peru Med Exp Salud Publica. 2011;28(4):589-94.

Molero AE P-RrG, Maestre GE. Modulation by age and gender of risk for Alzheimer's disease and vascular dementia associated with the apolipoprotein E-ε4 allele in Latin Americans: findings from the Maracaibo Aging Study. Neuroscience letters. 2001;307(1):5-8. doi: 10.1016/S0304-3940(01)01911-5

Arráiz N, Bermudez V, Prieto C, Sánchez MP, Escalona C, Sanz E, Rondón N, Reyes F, Velasco M. Association between apoliprotein E gene polymorphism and hypercholesterolemic phenotype in Maracaibo, Zulia state, Venezuela. Am J Ther. 2010;17(3):330-6. doi: 10.1097/MJT.0b013e3181c1235d.

Paz-y-Miño C CC, López-Cortés A, Munoz MJ, Cumbal N, Castro B, Cabrera A, Sánchez ME. Genetic polymorphisms in apolipoprotein E and glutathione peroxidase 1 genes in the Ecuadorian population affected with Alzheimer's disease. Am J Med Sci. 2010;340(5):373-7. doi: 10.1097/MAJ.0b013e3181e93475

Souza DR, De Godoy MR, Hotta J, Tajara EH, Brandao AC, Pinheiro Júnior S, Tognola WA, Dos Santos JE. Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians. Braz J Med Biol Res. 2003;36(7):919-23. doi: 10.1590/s0100-879x2003000700013

De França E, Alves JG, Hutz MH. Apolipoprotein E polymorphism and its association with serum lipid levels in Brazilian children. Human Biol. 2004;76(2):267-75.

Fuzikawa AK PS, Taufer M, Moriguchi EH, Lima-Costa MF. Apolipoprotein E polymorphism distribution in an elderly Brazilian population: the Bambuí Health and Aging Study. Braz J Med Biol Res. 2007;40(11):1429-34. doi: 10.1590/s0100-879x2007001100002.

Brito DD, Fernandes AP, Gomes KB, Coelho FF, Cruz NG, Sabino AP, Cardoso JE, Figueiredo-Filho PP, Diamante R, Norton CR, Sousa MO. Apolipoprotein A5-1131T> C polymorphism, but not APOE genotypes, increases susceptibility for dyslipidemia in children and adolescents. Molecular Biology Reports. 2011;38(7):4381-8. doi: 10.1007/s11033-010-0565-5

Gayà‐Vidal M AG, Carreras‐Torres R, Via M, Esteban E, Villena M, Vasquez R, Dugoujon JM, Moral P. Apolipoprotein E/C1/C4/C2 gene cluster diversity in two native Andean populations: Aymaras and Quechuas. Annals Hum Genet. 2012;76(4):283-95. doi: 10.1111/j.1469-1809.2012.00712.x

Quiroga P, Calvo C, Albala C, Urquidi J, Santos JE, Perez H, Klaassen G. Apolipoprotein E polymorphism in elderly Chilean people with Alzheimer’s disease. Neuroepidemiology. 1998;18(1):48-52. doi: 10.1159/000026195

Rollan A, Loyola G, Covarrubias C, Giancaspero R, Acevedo K, Nervi F. Apolipoprotein E polymorphism in patients with acute pancreatitis. Pancreas. 1994;9(3):349-53. doi: 10.1097/00006676-199405000-00011

Leiva E, Mujica V, Orrego R, Prieto M, Arredondo M. Apolipoprotein E polymorphism in type 2 diabetic patients of Talca, Chile. Diabetes research and clinical practice. 2005;68(3):244-9. doi: 10.1016/j.diabres.2004.09.017

Pedraza OL Camacho I, Sierra FA, Rubio-Gómez C, Salazar AM, Montalvo C, Morillo D, Lozano A, Gutiérrez-Castañeda LD, Torres-Tobar L, Piñeros C. Association between ε4 allele, cardio-metabolic and social risk factors in the development of cognitive impairment in elderly adults from Bogota. Sometido a publicación.

Citado por