Association of apolipoprotein E polymorphism with plasma lipids and Alzheimer's disease in a Southern Brazilian population

Abstract

Apolipoprotein E (protein: apo E; gene: APOE) plays an important role in the multifactorial etiology of both Alzheimers disease (AD) and lipid level concentrations. The polymerase chain reaction (PCR) was used to investigate the APOE gene polymorphism in 446 unrelated Caucasians, among them 23 AD patients, and 100 Afro-Brazilians living in Porto Alegre, Brazil. The frequencies of the APOE*2, APOE*3 and APOE*4 alleles were 0.075, 0.810 and 0.115 in Caucasians and 0.075, 0.700 and 0.225 in Afro-Brazilians, respectively (c 2 = 8.72, P = 0.013). A highly significant association was observed between the APOE*4 allele and AD in this population-based sample. The APOE*4 frequency in AD patients (39%) was about four times higher than in the general Caucasian population (11.5%). The influence of each of the three common APOE alleles on lipid traits was evaluated by the use of the average excess statistic. The E*2 allele is associated with lower levels of triglycerides and of total and non-HDL cholesterol in both men and women. Conversely, the E*4 allele is associated with higher levels of these traits in women only. The effect of APOE alleles was of greater magnitude in women.

Association of apolipoprotein E polymorphism in late-onset Alzheimer's disease and vascular dementia in Brazilians

“…The ε4 allele frequency is approximately 7 to 16% and the ε2 allele frequency is 6.3 to 12% (6)(7)(8)(9)(10). Of these three, ε4 is recognized as a risk factor for LOAD, whereas the ε2 and ε3 alleles appear to enhance tolerance to the brain degenerative process, extending the survival of affected neurons.…”

“…In fact, many case-control and post-mortem studies of LOAD patients have shown ε4 allele frequencies ranging from 17 to 57% in both sporadic and familial cases (6)(7)(8)(9)16,17). The APOE genotype, also investigated in other types of dementias, has shown a slight association with VD, Pick's disease and Lewy's body disease but no association with Parkinson's disease or Creutzfeldt-Jakob disease (10,18).…”

Chapter 4 Alzheimer's Disease in Adults with Down Syndrome

“…The APOE gene, which occurs predominately in three variants or alleles [i.e., ε2, ε3, or ε4], is involved in cholesterol transport and lipid metabolism in plasma (Dupuy et al, 2001) as well as accumulation of beta-amyloid protein in the brains of typically developing elderly people, both with and without Alzheimer's disease (Lambert et al, 2001;Polvikowski et al, 1995]. In numerous studies, participants with Alzheimer's disease have been found to have higher frequencies of the APOE ε4 allele compared with those without other APOE genotypes, and those with the ε4 allele have an earlier age of onset of Alzheimer's disease (Corder et al, 1993;de-Andrade, Larrandaburu, Callegari-Jacques, Gastaldo, & Hutz, 2000;Isbir et al, 2001;Mayeux et al, 1993). APOE ε4 also is associated with greater deposition of beta-amyloid protein in the brains of adults with and without Down syndrome (Hyman, West, Rebeck, Lai, & Mann, 1995), and as for the typically developing population, increased risk for Alzheimer's disease has been associated with the presence of an ε4 allele (Deb et al, 2000;Prasher, Chowdhury, Rowe, & Bain, 1997;Schupf et al, 1996).…”

Apolipoproteína E e a doença de Alzheimer

“…de desenvolver DA do que parentes de mesmo grau de indivíduos classificados como caucasianos (Kim et al, 2002); um estudo feito na região sudeste do Brasil identificou uma forte associação entre apoE ε4 e DA. O alelo ε4 foi encontrado com uma freqüência de 39% em portadores da DA, valor cerca de quatro vezes maior que o encontrado nos indivíduos saudáveis da mesma localidade (de-Andrade et al, 2000). Um outro estudo com 126 indivíduos brasileiros (Souza et al, 2003) mostrou que a freqüência do alelo apoE ε2 foi consideravelmente menor no grupo de pacientes com DA (1%; n = 68); as freqüências do alelo apoE ε3 e do genótipo apoE ε3/ε3 foram maiores nos controles (84% e 72%, respectivamente; n = 58), enquanto as freqüências do alelo apoE ε4 e do genótipo apoE ε3/ε4 foram maiores nos indivíduos com DA (25% e 41%, respectivamente).…”

“…Perspectivas no estudo de apoE e DA Tabela 1 -Distribuição das freqüências alélicas e genotípicas do gene apoE na população brasileira, em indivíduos com a DA e indivíduos-controle, com base na somatória de genótipos definidos em dois estudos (de-Andrade et al, 2000;Souza et al, 2003) Apesar da contradição existente entre muitos estudos atuais, sabemos que o polimorfismo de apoE é apenas um dos diversos fatores genéticos envolvidos na DA. A apoE desempenha um papel importante na instauração da DA, mas o simples fato de um indivíduo possuir, mesmo que em homozigose, a isoforma ε4, não implica necessariamente o desenvolvimento da doença.…”