Association of rs6265 and rs2030324 polymorphisms in brain-derived neurotrophic factor gene with Alzheimer's disease: a meta-analysis

Abstract

Background: The association between polymorphisms rs6265 and rs2030324 in brain-derived neurotrophic factor (BDNF) and Alzheimer's disease (AD) has been widely reported, but the results remain controversial.

Methods: A comprehensive search of Pubmed, Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Med Online and China Biology Medical literature database (CBM) was performed. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using fixed or random-effects models. We excluded the studies with OR>3.0 or OR<0.3 for sensitive analysis. Subgroup analysis by ethnicity, form of AD and gender was carried out. Meta-regression was conducted to explore the potential sources of between-study heterogeneity.

Results: 29 articles with 7548 cases and 7334 controls concerning rs6265 and 22 articles with 5796 cases and 5706 controls concerning rs2030324 were included in this meta-analysis. The combined evidence suggested rs6265 contributing significantly to the increased risk of AD in females (codominant: fixed-effects model (FEM): OR = 1.13, 95% CI = 1.04-1.23; dominant: FEM: OR = 1.17, 95% CI = 1.05-1.31), especially for Caucasian females (codominant: FEM: OR = 1.18, 95% CI = 1.03-1.34; dominant: FEM: OR = 1.18, 95% CI = 1.01-1.37) and female late-onset Alzheimer's disease (LOAD) patients (codominant: FEM: OR = 1.22, 95% CI = 1.05-1.41; dominant: FEM: OR = 1.23, 95% CI = 1.03-1.46). No evidence indicated an association between rs2030324 with AD in codominant (random-effects model (REM): OR = 1.06, 95% CI = 0.89-1.26) and dominant (REM: OR = 1.05, 95% CI = 0.86-1.27) models.

Conclusion: This meta-analysis suggested A allele of rs6265 might increase the risk of AD in Caucasian females and female LOAD patients. In addition, no evidence indicated an association between rs2030324 with AD. Further studies are needed to confirm these results.

Figure 1. Flow diagram of literature search.

Figure 2. Forest plots of relationship between BDNF gene rs6265 polymorphism and AD risk in codominant model (A vs. G) for overall analysis.

White diamond donates the pooled OR. Black squares indicate the OR in each study, with square sizes inversely proportional to the standard error of the OR. Horizontal lines represent 95% CIs.

Figure 3. Forest plots of relationship between BDNF gene rs6265 polymorphism and AD risk in codominant model (A vs. G) for female group.

White diamond donates the pooled OR. Black squares indicate the OR in each study, with square sizes inversely proportional to the standard error of the OR. Horizontal lines represent 95% CIs.