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.
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.
Authors: Deborah Blacker; Lars Bertram; Aleister J Saunders; Thomas J Moscarillo; Marilyn S Albert; Howard Wiener; Rodney T Perry; Julianne S Collins; Lindy E Harrell; Rodney C P Go; Amy Mahoney; Terri Beaty; M Danielle Fallin; Dimitrios Avramopoulos; Gary A Chase; Marshal F Folstein; Melvin G McInnis; Susan S Bassett; Kimberly J Doheny; Elizabeth W Pugh; Rudolph E Tanzi Journal: Hum Mol Genet Date: 2003-01-01 Impact factor: 6.150
Authors: Elisabeth Tarkowski; Razao Issa; Magnus Sjögren; Anders Wallin; Kaj Blennow; Andrej Tarkowski; Pat Kumar Journal: Neurobiol Aging Date: 2002 Mar-Apr Impact factor: 4.673
Authors: Majid Shahbazi; Anthony A Fryer; Vera Pravica; Iain J Brogan; Helen M Ramsay; Ian V Hutchinson; Paul N Harden Journal: J Am Soc Nephrol Date: 2002-01 Impact factor: 10.121
Authors: D F Stroup; J A Berlin; S C Morton; I Olkin; G D Williamson; D Rennie; D Moher; B J Becker; T A Sipe; S B Thacker Journal: JAMA Date: 2000-04-19 Impact factor: 56.272
Authors: B Oosthuyse; L Moons; E Storkebaum; H Beck; D Nuyens; K Brusselmans; J Van Dorpe; P Hellings; M Gorselink; S Heymans; G Theilmeier; M Dewerchin; V Laudenbach; P Vermylen; H Raat; T Acker; V Vleminckx; L Van Den Bosch; N Cashman; H Fujisawa; M R Drost; R Sciot; F Bruyninckx; D J Hicklin; C Ince; P Gressens; F Lupu; K H Plate; W Robberecht; J M Herbert; D Collen; P Carmeliet Journal: Nat Genet Date: 2001-06 Impact factor: 38.330