title: Vascular endothelial growth factor gene promoter polymorphisms and Alzheimer's disease risk: a meta-analysis.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Guangdong Key Laboratory of Age-Related Cardiac and Cerebral Diseases, Affiliated Hospital of Guangdong Medical College, Zhanjiang, China.
authors.forename: Sheng-Yuan
authors.initials: SY
authors.lastname: Liu
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Zeng
authors.forename: Zhong-Wei
authors.initials: ZW
authors.lastname: Chen
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Wang
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Ke-Shen
authors.initials: KS
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000175:diagnosis / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics; D016001:Confidence Intervals; D003627:Data Interpretation, Statistical; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; D042461:Vascular Endothelial Growth Factor A