-1154G/A and -2578C/A polymorphisms of the vascular endothelial growth factor gene in Tunisian Alzheimer patients in relation to beta-amyloid (1-42) and total tau protein.
ABSTRACT Recent evidences indicate that polymorphisms within the promoter region of the vascular endothelial growth factor (VEGF) gene may elevate the risk for Alzheimer's disease (AD). To further investigate, we have analyzed association between promoter polymorphisms of the VEGF gene in 93 AD patients and age and sex matched 113 controls from Tunisian population. The distribution of genotype and allele frequencies of the VEGF (-2578C/A) and (-1154G/A) polymorphisms did not differ significantly between AD and control groups (p>0.05). In the subgroup of ApoE varepsilon4 carriers, the -2578A was observed to be significantly higher in the AD patients than in the control individuals. After adjusting the data by gender, age and the ApoE varepsilon4 status using logistic regression, the -2578A allele was found to increase the risk for sporadic AD by 1.7-fold. The present study provides the evidence that the -2578A allele may be associated with the development of AD in the individuals with ApoE varepsilon4 allele. In addition, AD patients carrying the -2578A allele had lower Abeta42 (p=0.029) levels than those without this allele, particularly in subjects with ApoE varepsilon4 allele.
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ABSTRACT: Dementia is a major problem of health in developed societies. Alzheimer's disease (AD), vascular dementia, and mixed dementia account for over 90% of the most prevalent forms of dementia. Both genetic and environmental factors are determinant for the phenotypic expression of dementia. AD is a complex disorder in which many different gene clusters may be involved. Most genes screened to date belong to different proteomic and metabolomic pathways potentially affecting AD pathogenesis. The ε4 variant of the APOE gene seems to be a major risk factor for both degenerative and vascular dementia. Metabolic factors, cerebrovascular disorders, and epigenetic phenomena also contribute to neurodegeneration. Five categories of genes are mainly involved in pharmacogenomics: genes associated with disease pathogenesis, genes associated with the mechanism of action of a particular drug, genes associated with phase I and phase II metabolic reactions, genes associated with transporters, and pleiotropic genes and/or genes associated with concomitant pathologies. The APOE and CYP2D6 genes have been extensively studied in AD. The therapeutic response to conventional drugs in patients with AD is genotype specific, with CYP2D6-PMs, CYP2D6-UMs, and APOE-4/4 carriers acting as the worst responders. APOE and CYP2D6 may cooperate, as pleiotropic genes, in the metabolism of drugs and hepatic function. The introduction of pharmacogenetic procedures into AD pharmacological treatment may help to optimize therapeutics.International journal of Alzheimer's disease. 01/2012; 2012:518901.
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ABSTRACT: AIM: Conclusions on the association between polymorphisms in the vascular endothelial growth factor (VEGF) gene promoter and risk of Alzheimer's disease (AD) are ambiguous, and sufficient evaluation of the association is lacking. Therefore, we performed a meta-analysis of observational studies to explore the association between polymorphisms in the VEGF gene promoter and AD risk. METHODS: Bibliographical searches were performed in the MEDLINE, EMBASE, and China National Knowledge Infrastructure (CNKI) databases without any language limitations. Three investigators independently assessed abstracts for relevant studies and independently reviewed all eligible studies. A meta-analysis was conducted using a fixed- or random-effects model. Odds ratios (ORs) and their 95% confidence intervals (CIs) were used to assess the strength of association. All statistical analyses were performed using Stata 11.0 software. RESULTS: The meta-analysis of 2787 AD cases and 2841 controls from eight published case-control studies on the -2578C/A polymorphism and 1422 AD cases and 1063 controls from four studies on the -1154G/A polymorphism did not show any significant associations. However, in a subgroup analysis stratified by the presence of APOE є4, associations were observed with APOE ε4 (-) for -2578C/A (A vs. C: OR = 1.22, 95% CI = 1.04-1.43, P = 0.014; A/A vs. C/C: OR = 1.59, 95% CI = 1.11-2.27, P = 0.011 and A/A vs. A/C + C/C: OR = 1.46, 95% CI = 1.08-1.99, P = 0.015) and -1154G/A (A vs. G: OR = 0.74, 95% CI = 0.62-0.89, P = 0.001; A/A vs. G/G: OR = 0.57, 95% CI = 0.37-0.87, P = 0.009; A/G vs. G/G: OR = 0.69, 95% CI = 0.53-0.89, P = 0.004 and A/A + A/G vs. G/G: OR = 0.66, 95% CI = 0.52-0.85, P = 0.001). CONCLUSION: This meta-analysis showed the risk role of the -2578 polymorphism and the protective role of the -1154 polymorphism when the APOE є4 status was negative, suggesting that the two polymorphisms in the VEGF promoter may have opposing effects on AD risk in an APOE є4-independent manner.CNS Neuroscience & Therapeutics 04/2013; · 4.46 Impact Factor
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ABSTRACT: There were conflicting results about whether promoter polymorphisms (-2578C/A, -1154G/A) of Vascular Endothelial Growth Factor (VEGF) gene is a risk factor of Alzheimer's disease (AD). To determine the relationship between them, a meta-analysis is needed urgently. We searched all the reports about VEGF promoter polymorphisms (-2578C/A, -1154G/A) and AD risk from PubMed, Web of Science, Cochrane Collaboration and Google Scholar database for the period up to 1 August, 2012, a total of 7 studies containing 2731AD patients and 2442 controls were included. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated applying fixed or random effects models. There was no significant association between VEGF-2578C/A polymorphisms and AD risk in all gene models (OR =1.08, 95% CI=0.94-1.23 for A vs. C; OR =1.19, 95% CI=0.89-1.59 for AA vs. CC; OR =1.15, 95% CI=0.91-1.45 for AA vs. CC+CA; OR =1.11, 95% CI=0.98-1.25 for AA+CA vs. CC). Similar results were provided in subgroup analysis by ethnicity. For the VEGF-1154G/A polymorphisms, lack of an association was also found (A vs. G: OR=0.89, 95% CI=0.79-1.01; AA vs. GG: OR =0.82, 95% CI=0.62-1.08; AA vs. GA+GG: OR =0.89, 95% CI=0.68-1.16; AA+AG vs. GG: OR =0.85, 95% CI=0.72-1.00). Conclusively, the result of this meta-analysis suggested that VEGF promoter polymorphisms (-2578C/A, -1154G/A) might not contribute to the susceptibility of AD.Gene 01/2013; · 2.20 Impact Factor