Skip to main content

Advertisement

SpringerLink
Log in

Genetic Influences on Alzheimer’s Disease: Evidence of Interactions Between the Genes APOE, APOC1 and ACE in a Sample Population from the South of Brazil

  • Original Paper
  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

Alzheimer’s disease is a complex neurodegenerative disorder. Several genes have been suggested as Alzheimer’s susceptibility factors, the apolipoprotein E (APOE) gene being an established susceptibility gene and the genes coding angiotensin-converting enzyme (ACE) and apolipoprotein C1 (APOC1) being considered possible candidate genes for the disease. The objective of this study was to investigate the association of ACE and APOC1 gene polymorphisms with susceptibility to Alzheimer’s disease and dementia in general, both alone and combined with the APOE gene. Forty-seven patients with dementia in general (35 of them with Alzheimer’s disease) and 85 controls were investigated. The haplotypes E*3/−317*ins and E*4/−317*ins of APOE/APOC1 genes were significantly more frequent in the groups with Alzheimer′s disease and dementia in general (P < 0.001). The frequency of the ACE*ins allele was also greater in the groups with Alzheimer’s disease and dementia in general (P = 0.022; P = 0.045), but genotype frequencies were only different in groups without the E*4/−317*ins haplotype (P = 0.012 for Alzheimer’s disease; P = 0.04 for dementia). Our data point to important genetic interactions involved in these diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Farrer LA, Cupples LA, Haines JL et al (1997) 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. J Am Med Soc 278:1349–1356

    CAS  Google Scholar 

  2. De Andrade FM, Larrandaburu M, Callegari-Jacques SM et al (2000) Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer’s disease in a Southern Brazilian population. Br J Med Biol Res 33:529–537

    Google Scholar 

  3. Mahley RW, Rall SC Jr (2000) Apolipoprotein E: far more than a lipid transport protein. Annu Rev Genomics Hum Genet 1:507–537

    Article  PubMed  CAS  Google Scholar 

  4. Ki CS, Na DL, Kim DK et al (2002) Genetic association of an apolipoprotein C-I (APOC1) gene polymorphism with late-onset Alzheimer′s disease. Neurosci Lett 319:75–78

    Article  PubMed  CAS  Google Scholar 

  5. Poduslo SE, Neal M, Schwankhaus J (1995) A closely linked gene to apolipoprotein E may serve as an additional risk factor for Alzheimer′s disease. Neurosci Lett 201:81–83

    Article  PubMed  CAS  Google Scholar 

  6. Drigalenko E, Poduslo S, Elston R (1998) Interaction of the apolipoprotein E and CI loci in predisposing to late-onset Alzheimer′s disease. Neurology 51:131–135

    PubMed  CAS  Google Scholar 

  7. Retz W, Thome J, Durany N et al (2001) Potential genetic markers of sporadic Alzheimer′s dementia. Psychiatr Genet 11:115–122

    Article  PubMed  CAS  Google Scholar 

  8. Oliveira JR, Lima Filho JL, Shimokomaki CM (1997) The use of apolipoprotein E genotype for preclinical detection of risk groups for Alzheimer’s disease. Am J Med Genet 74:216–217

    Article  PubMed  CAS  Google Scholar 

  9. Phillips MI, Oliveira EM (2008) Brain renin angiotensin in disease—a review. J Mol Med 86:715–722

    Article  PubMed  CAS  Google Scholar 

  10. Yang YH, Liu CK (2008) Angiotensin- converting enzyme gene in Alzheimer’s disease. J Exp Med 215:295–298

    CAS  Google Scholar 

  11. Alvarez R, Alvarez V, Lahoz CH et al (1999) Angiotensin converting enzyme and endothelial nitric oxide synthase DNA polymorphism and late onset Alzheimer’s disease. J Neurol Neurosurg Psychiatry 67:733–736

    Article  PubMed  CAS  Google Scholar 

  12. Bartrés-Faz D, Junqué C, Clemente IC et al (2001) MRI and genetic correlates of cognitive function in elders with memory impairment. Neurobiol Aging 22:449–459

    Article  PubMed  Google Scholar 

  13. Mckinley MJ (2003) The brain renin—angiotensin system: location and physiological roles. Int J Biochem Cell Biol 35:901–918

    Article  PubMed  CAS  Google Scholar 

  14. Lehmann DJ, Cortina-Borja M, Warden DR et al (2005) Large meta-analysis establishes the ACE insertion-deletion polymorphism as a marker of Alzheimer’s disease. Am J Epidemiol 162:305–317

    Article  PubMed  Google Scholar 

  15. Mckhann G, Drachman D, Folstein M et al (1984) Clinical diagnosis of Alzheimer’s disease. Report of the NINCDS-ADRA Work Group under the auspices of departments of health and human services task force on Alzheimer’s disease. Neurology 34:939–944

    PubMed  CAS  Google Scholar 

  16. Lahiri DK, Nurnberger JI (1991) A rapid non-enzymatic method for the preparation of HMW DNA from blood for RFLP studies. Nucleic Acids Res 19:5444

    Article  PubMed  CAS  Google Scholar 

  17. Franken AR, Bellesso M, Cavazin AM et al (2004) Associação do polimorfismo do gene da enzima conversora da angiotensina com dados ecocardiográficos em jovens normotensos filhos de hipertensos. Rev Assoc Med Bras 50:62–67

    Article  PubMed  Google Scholar 

  18. Maekawa B, Cole TG, Seip RL et al (1995) Apolipoprotein E genotyping methods for the clinical laboratory. J Clin Lab Anal 9:63–69

    Article  PubMed  CAS  Google Scholar 

  19. Nillesen WM, Smeets HJ, van-Oost BA (1990) Human ApoCI HpaI restriction site polymorphism revealed by the polymerase chain reaction. Nucleic Acids Res 18:3428

    Article  PubMed  CAS  Google Scholar 

  20. Abramson JH, Gahlinger PM (2001) Computer programs for epidemiologists: PEPI, version 4.0. Sagebrush Press, Salt Lake City

    Google Scholar 

  21. Schneider S, Roessli D, Excoffier L (2000) Arlequin ver. 2.000: A software for population genetics data analysis. Genetics and Biometry Laboratory, University of Geneva, Switzerland

    Google Scholar 

  22. Long JC (1999) Multiple locus haplotype analysis, version 2.0. Software and documentation distributed by the author. Section on population genetics and linkage, laboratory of neurogenetics, NIAAA. National Institutes of Health, Bethesda

    Google Scholar 

  23. Takei N, Miyashita A, Tsukie T et al (2009) Genetic association study on in and around the APOE in late-onset Alzheimer disease in Japanese. Genomics 93:441–448

    Article  PubMed  CAS  Google Scholar 

  24. Chuang W-L, Hsieh Y-C, Wang C-Y et al (2010) Association of apolipoproteins E4 and C1 with onset age and memory: A study of sporadic Alzheimer disease in Taiwan. J Geriatr Psychiatry Neurol 23:42–48

    Article  PubMed  Google Scholar 

  25. Study P, Lapworth R, Bird R (1983) Angiotensin-converting enzyme and its clinical significance–a review. J Clin Pathol 36:938–947

    Article  Google Scholar 

  26. Xia H, Lazartigues E (2008) Angiotensin converting enzyme 2 in the brain: properties and future directions. J Neurochem 107:1482–1494

    Article  PubMed  CAS  Google Scholar 

  27. Kehoe PG, Katzov H, Feuk L et al (2003) Haplotypes extending across ACE are associated with Alzheimer’s disease. Hum Mol Genet 12:859–867

    Article  PubMed  CAS  Google Scholar 

  28. Tian J, Shi J, Bailey K et al (2004) A polymorphism in the angiotensin 1-converting enzyme gene is associated with damage to cerebral cortical white matter in Alzheimer’s disease. Neurosci Lett 354:103–106

    Article  PubMed  CAS  Google Scholar 

  29. Wang B, Jin F, Yang Z et al (2006) The insertion polymorphism in angiotensin-converting APOE 4 Allele increases enzyme gene associated with the risk of late-onset Alzheimer disease. J Mol Neurosci 30:267–271

    Article  PubMed  CAS  Google Scholar 

  30. Helbecque N, Codron V, Cottel D et al (2009) Na age effect on the association of common variants of ACE with Alzheimer’s disease. Neurosci Lett 461:181–184

    Article  PubMed  CAS  Google Scholar 

  31. Ribizzi G, Fiordoro S, Barocci S et al (2010) Cytokine polymorphisms and Alzheimer disease: possible associations. Neurol Sci 31:321–325

    Article  PubMed  CAS  Google Scholar 

  32. Schjeide BMM, McQueen MB, Mullin K et al (2009) Assessment of Alzheimer’s disease case—control associations using family-based methods. Neurogenetics 10:19–25

    Article  PubMed  Google Scholar 

  33. Monastero R, Caldarella R, Mannino M et al (2002) Lack of association between angiotensin converting enzyme polymorphism and sporadic Alzheimer’s disease. Neurosci Lett 335:147–149

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Health Science Institute, Pró-Reitoria de Pesquisa e Inovação, PROPI Sala 201 F, Universidade Feevale, RS 239, No. 2755, B. Vila Nova, Novo Hamburgo, RS, 93352-000, Brazil

    Juliana Fagion Lucatelli, Alessandra Chielle Barros, Vanessa Kappel da Silva, Fernanda da Silva Machado, Pâmela Camini Constantin & Fabiana Michelsen de Andrade

  2. Clinical Medicine Department, Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil

    Ana Amélia Cipriani Dias

  3. Department of Genetics, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil

    Mara Helena Hutz

Authors
  1. Juliana Fagion Lucatelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessandra Chielle Barros
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Vanessa Kappel da Silva
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fernanda da Silva Machado
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Pâmela Camini Constantin
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana Amélia Cipriani Dias
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Mara Helena Hutz
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Fabiana Michelsen de Andrade
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fabiana Michelsen de Andrade.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lucatelli, J.F., Barros, A.C., Silva, V.K.d. et al. Genetic Influences on Alzheimer’s Disease: Evidence of Interactions Between the Genes APOE, APOC1 and ACE in a Sample Population from the South of Brazil. Neurochem Res 36, 1533–1539 (2011). https://doi.org/10.1007/s11064-011-0481-7

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11064-011-0481-7

Keywords

Search

Navigation