RESUMO
The genetics of Alzheimer's disease (AD) is complex. Three genes (amyloid precursor protein, presenilin 1 and presenilin 2) have been described in the relatively rare, early-onset, autosomal dominant familial form of AD. In the common, non-familial (sporadic) late-onset AD, the major known genetic risk factor is the epsilon4 allele of the apolipoprotein E (APOE) gene. However, at least half of the people who develop AD do not carry this allele, and not all people who do carry this allele develop AD even if they live to an old age. Therefore, approximately 30 other candidate genes involving a protein in a critical pathway in the pathogenesis of disease (principally interaction with amyloid-beta, oxidative stress and inflammation/apoptosis) have been considered as risk factors for sporadic AD. Then these genes have been sequenced in search of genetic variability or polymorphisms, and each putative polymorphism has been reported to alter the risk of AD either directly or by an interaction with the APOE epsilon4 allele. However, positive-association studies with these candidate genes have not been consistently confirmed.
Assuntos
Doença de Alzheimer/genética , Precursor de Proteína beta-Amiloide/genética , Apolipoproteínas E/genética , Proteínas de Membrana/genética , Estresse Oxidativo/genética , Idade de Início , Doença de Alzheimer/etiologia , Apolipoproteínas E/metabolismo , Apoptose , Butirilcolinesterase/genética , Catepsina D/genética , Humanos , Polimorfismo Genético , Presenilina-1 , Presenilina-2 , Fatores de RiscoRESUMO
Homozygosity for the A allele of the -491 A/T apolipoprotein E (APOE) promoter polymorphism has recently been reported to be associated with sporadic Alzheimer's disease (AD). Two hundred and fifty one patients with AD and an equal number of controls derived from the same region in a Spanish population, were genotyped for -491 A/T and epsilon2/epsilon3/epsilon4 APOE polymorphisms. We did not detect an elevated -491 AA genotype frequency when comparing AD cases to controls. In contrast, persons homozygous for the T allele were at a significantly reduced risk of AD (odds ratio of 0.10, P=0.006). Multiple logistic regression analysis indicated that the -491 TT polymorphism added information on the risk of AD which was independent of that of the APOE epsilon4 allele.
Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Predisposição Genética para Doença , Polimorfismo Genético/fisiologia , Regiões Promotoras Genéticas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Feminino , Frequência do Gene , Genótipo , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Valores de ReferênciaRESUMO
INTRODUCTION: Recent reports indicate that the K variant of the butyrylcholinesterase (BCHE) gene may act in synergism with the epsilon4 allele of apolipoprotein E (APOE) to increase the risk of Alzheimer's disease (AD), but this is controversial. MATERIAL AND METHODS: We genotyped for the BCHE-K and APOE epsilon4 alleles in a sample of 249 AD patients and 250 controls derived from the same region in a Spanish population. RESULTS: A protective effect of the K variant of BCHE with an odds ratio of 0.41 (95% confidence interval 0.19-0.86, P=0.02) was observed among non-APOE epsilon4 carriers, but it was limited to women. CONCLUSION: Our study is the first to demonstrate that lower susceptibility to AD determined by the K variant of BCHE is dependent on gender.
Assuntos
Doença de Alzheimer/genética , Doença de Alzheimer/fisiopatologia , Apolipoproteínas E/genética , Butirilcolinesterase/genética , Predisposição Genética para Doença , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
An association between cognitive performance in elderly people and variability in the codon 129 of the prion protein gene (PRNP) has been recently described. The authors analyzed this polymorphism in 278 sporadic AD patients and 268 cognitively normal control subjects. Analyses stratifying by APOE genotype, age, and gender failed to reveal any association between homozygosity for the 129 PRNP methionine or valine alleles and AD.
Assuntos
Doença de Alzheimer/genética , Amiloide/genética , Polimorfismo Genético/genética , Precursores de Proteínas/genética , Idade de Início , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/epidemiologia , Substituição de Aminoácidos/genética , Apolipoproteína E4 , Apolipoproteínas E/genética , Feminino , Triagem de Portadores Genéticos , Ligação Genética/genética , Predisposição Genética para Doença/epidemiologia , Homozigoto , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Proteínas Priônicas , Príons , Medição de Risco , Espanha/epidemiologia , População Branca/genéticaRESUMO
We examined the possible involvement of polymorphisms of the presenilin 1 (PS1) and presenilin 2 (PS2) genes in the risk for sporadic Alzheimer's disease (AD), either through an independent effect or through interaction with the existing apolipoprotein E (ApoE) risk, in 211 AD cases and 188 age-matched control subjects. No significant differences were obtained in any of the comparisons relating the effect of the PS1 and PS2 polymorphisms; thus, these polymorphisms do not appear to be sufficient risk factors by themselves for sporadic AD. Although the ApoE varepsilon4 genotype is the only definite predictor of risk, homozygosity for either the 1 allele of the PS1 or the C allele of the PS2 genes may increase the risk conferred by the presence of an ApoE epsilon4 allele. Additionally, combination of PS1/11 and PS2/CC genotypes might have a small synergistic effect on the risk for AD.
