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

PLoS One. 2014 Apr 14;9(4):e94961. doi: 10.1371/journal.pone.0094961. eCollection 2014.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Female
  • Gene Frequency / genetics
  • Genetic Association Studies*
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Models, Genetic
  • Polymorphism, Single Nucleotide / genetics*
  • Publication Bias
  • Risk Factors
  • White People / genetics

Substances

  • Brain-Derived Neurotrophic Factor

Grants and funding

This study was supported by the National Natural Science Foundation of China (grant # 31371024). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.