Open AccessVascular Endothelial Growth Factor Gene Promoter Polymorphisms and Alzheimer's Disease Risk: A Meta‐Analysis
Author(s) -
Liu ShengYuan,
Zeng FangFang,
Chen ZhongWei,
Wang ChangYi,
Zhao Bin,
Li KeShen
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12093
Subject(s) - meta analysis , odds ratio , confidence interval , subgroup analysis , medicine , apolipoprotein e , oncology , case control study , observational study , bioinformatics , polymorphism (computer science) , disease , gene , allele , genetics , biology
Summary Aim Conclusions on the association between polymorphisms in the vascular endothelial growth factor ( VEGF ) gene promoter and risk of A lzheimer'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 C hina N ational K nowledge I nfrastructure ( 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 ( OR s) and their 95% confidence intervals ( CI s) 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.