RESUMO
It is now well established that vascular risk factors are associated with cognitive performances. The renin-angiotensin system (RAS) components, major determinants of the cardiovascular system, are expressed in the brain and were shown to play a role on amyloid metabolism, learning and memory. The angiotensin-converting enzyme (ACE), a pivotal RAS protein, is encoded by a huge gene containing many variants, one of them, the I/D variant (rs1799752), being associated with Alzheimer's disease (AD). Other variants, such as SNPs rs4291A>T located -240bp from the initiation codon, and rs4343G>A encoding a silent mutation in exon 16, were inconsistently associated with the risk of AD. In a case-control study including 376 late-onset AD patients and 444 control subjects, we showed a statistically significant effect on the risk of AD of two variants (rs4343 and rs1799752) and of the haplotype ATI (rs4343/rs4291/rs1799752) in subjects aged 73 years and above.
Assuntos
Doença de Alzheimer/genética , Renina/genética , Fatores Etários , Idade de Início , Idoso , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Masculino , Polimorfismo Genético , População BrancaRESUMO
BACKGROUND/AIMS: Accumulating biological and epidemiological evidence suggests a close link between cholesterol metabolism and the pathophysiology of Alzheimer's disease (AD). The observation that the use of statins reduces the risk of AD sustains this hypothesis. Apolipoprotein A-I (APOA1) is the major component of the high-density lipoproteins, particles involved in reverse cholesterol transport. Therefore, genetic polymorphisms in the gene encoding APOA1 might influence cholesterol metabolism and be a risk factor for AD. A previous study suggested an impact of a G-->A polymorphism at position -75 bp in the APOA1 gene on the risk for early-onset AD and on the age at onset of the disease. We studied this polymorphism in 3 independent European population samples. METHODS: Genotyping was conducted asdescribed in the previous study. RESULTS: We were unable to show any impact of this polymorphism on the risk of AD. Conversely, subjects bearing the A allele of this polymorphism were at risk of cognitive decline. CONCLUSION: Our resultssuggest an impact of the G-->A polymorphism at position -75 bp in the APOA1 gene on cognitive impairment, but not on the risk of AD.
Assuntos
Doença de Alzheimer/genética , Apolipoproteína A-I/genética , Transtornos Cognitivos/genética , Polimorfismo Genético/genética , Regiões Promotoras Genéticas/genética , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Cromossomos Humanos Par 11/genética , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/epidemiologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Fatores de Risco , Índice de Gravidade de Doença , População Branca/genéticaRESUMO
OBJECTIVE: The goal of the present study was to assess the impact of 4 single nucleotide polymorphisms (SNPs) of APOA5/A4/C3 gene cluster on lipid levels and coronary heart disease (CHD) risk in French men. METHODS: A total of 442 men with CHD were recruited from the university hospital and compared to 475 men free of CHD from the population of the same geographical area. The APOA5 S19W, APOA5 -l2,238T>C, APOA4 T347S and APOC3 -482C>T SNPs were examined. RESULTS: The APOA5 S19W polymorphism was associated with plasma triglyceride levels. In multivariate logistic regression analyses the odds ratio (OR [95% Cl]) of hypertriglyceridemia (3rd vs. 1st tertile of triglyceride distribution) was 3.60 [1.38-9.42] in control subjects bearing at least one APOA5 19W variant. Haplotype analyses revealed a significant association between the 2111 haplotype and high triglyceride levels (+1.94 +/- 0.63 vs. 0.74 +/- 0.36 mmol/l for the 1111 haplotype p < 0.002). There was, in contrast, no significant difference in SNP distribution between CHD patients and controls. The age-adjusted OR of CHD were 1.46 [0.96-2.23], 0.79 [0.60-1.05], 0.91 [0.69-1.21] and 0.91 [0.69-l.22] in carriers of the APOA5 19W, APOA5 -12,238C, APOA4 347S and APOC3 -482T variants, respectively. There was also no significant difference in APOA5/A4/C3 haplotype distribution in patients and controls. CONCLUSION: The APOA5 19W variant is associated with increased plasma triglycerides. However, there is no evidence that APOA5 S19W, -12,238T > C, APOA4 T347S and APCC3 -482C > T SNPs are major risk factors of CHD in French men.
Assuntos
Apolipoproteínas A/sangue , Apolipoproteínas C/sangue , Colesterol/sangue , Doença das Coronárias/genética , Polimorfismo de Nucleotídeo Único , Triglicerídeos/sangue , Adulto , Apolipoproteína A-V , Apolipoproteínas , Apolipoproteínas A/genética , Apolipoproteínas C/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Colesterol/genética , HDL-Colesterol/sangue , HDL-Colesterol/genética , Doença das Coronárias/epidemiologia , França/epidemiologia , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/genéticaRESUMO
Several clinical and epidemiological studies suggest that Alzheimer's disease (AD) and vascular dementia share common risk factors. Oxidative stress is one of these well recognized factors. It can result from an excess of free-radical activity and impaired antioxidant defenses. Paraoxonase (PON1), a component of high density lipoproteins, has antioxidative potential and was previously associated with an increased risk of cardiovascular diseases. The impact of two polymorphisms in PON1 (Gln192Arg associated with enzyme activity and T-107C associated with enzyme concentration) was examined in a case-control study. The two polymorphisms were independent risk factors for nonAD dementia, particularly in APOE-4 noncarriers. An at-'risk haplotype' could be constructed including the Gln192 and the T-107 alleles, suggesting that subjects at risk have lower plasma paraoxonase levels and this enzyme is less active.