title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Epidemiology and Health Statistics, Medical College of Qingdao University, Qingdao, Shandong, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Department of Epidemiology and Health Statistics, Medical College of Qingdao University, Qingdao, Shandong, People's Republic of China.
authors.forename: Shuo
authors.initials: S
authors.lastname: Cheng
authors.affiliation: Department of Epidemiology and Health Statistics, Medical College of Qingdao University, Qingdao, Shandong, People's Republic of China.
authors.forename: Zhutian
authors.initials: Z
authors.lastname: Xie
authors.affiliation: Department of Epidemiology and Health Statistics, Medical College of Qingdao University, Qingdao, Shandong, People's Republic of China.
authors.forename: Dongfeng
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017594:Publication Bias; D012307:Risk Factors; D044465:White People / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor
references.citation: Trends Genet. 2004 Sep;20(9):439-44
references.pmid: 15313553
references.citation: Int J Epidemiol. 2007 Apr;36(2):439-45
references.pmid: 17182636
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2005 Apr 5;134B(1):1-5
references.pmid: 15635706
references.citation: Exp Neurol. 2005 Jul;194(1):91-6
references.pmid: 15899246
references.citation: Int J Epidemiol. 2006 Jun;35(3):572-8; discussion 593-6
references.pmid: 16540537
references.citation: J Alzheimers Dis. 2012;31(2):243-51
references.pmid: 22596272
references.citation: Dement Geriatr Cogn Disord. 2004;18(1):55-8
references.pmid: 15084795
references.citation: J Med Genet. 2007 Feb;44(2):e66
references.pmid: 17293537
references.citation: Brain Res Mol Brain Res. 1997 Oct 3;49(1-2):71-81
references.pmid: 9387865
references.citation: J Alzheimers Dis. 2008 Sep;15(1):61-70
references.pmid: 18780967
references.citation: Neurology. 1993 Aug;43(8):1467-72
references.pmid: 8350998
references.citation: Neurobiol Aging. 2011 Aug;32(8):1443-51
references.pmid: 19889475
references.citation: J Clin Psychiatry. 2008 Jul;69(7):1104-11
references.pmid: 18505307
references.citation: Mol Psychiatry. 2001 Jan;6(1):83-6
references.pmid: 11244490
references.citation: Rejuvenation Res. 2013 Feb;16(1):57-66
references.pmid: 23215636
references.citation: Stat Med. 2002 Jun 15;21(11):1539-58
references.pmid: 12111919
references.citation: Lancet. 1998 Jan 10;351(9096):123-7
references.pmid: 9439507
references.citation: J Neural Transm (Vienna). 2005 May;112(5):703-11
references.pmid: 15375678
references.citation: Folia Neuropathol. 2006;44(1):12-6
references.pmid: 16565926
references.citation: Nat Rev Neurol. 2011 Mar;7(3):137-52
references.pmid: 21304480
references.citation: Genes Brain Behav. 2009 Feb;8(1):43-52
references.pmid: 18786162
references.citation: Am J Hum Genet. 1999 Sep;65(3):664-70
references.pmid: 10441572
references.citation: J Neurochem. 2004 Dec;91(6):1312-21
references.pmid: 15584908
references.citation: Neurosci Lett. 2005 Jun 24;381(3):275-8
references.pmid: 15896483
references.citation: Mol Psychiatry. 2005 Sep;10(9):809-10
references.pmid: 15970929
references.citation: Mov Disord. 2005 Aug;20(8):1031-3
references.pmid: 15838855
references.citation: Mol Psychiatry. 2002;7(7):782-5
references.pmid: 12192623
references.citation: Neurosci Lett. 2005 Oct 14;387(1):11-6
references.pmid: 16054753
references.citation: Alzheimer Dis Assoc Disord. 2009 Jul-Sep;23(3):224-8
references.pmid: 19812463
references.citation: Br J Ophthalmol. 2009 Oct;93(10):1401-6
references.pmid: 19628492
references.citation: Ann Neurol. 2004 Mar;55(3):447-8
references.pmid: 14991827
references.citation: J Neurosci. 2006 Dec 6;26(49):12748-57
references.pmid: 17151278
references.citation: J Neural Transm Suppl. 2002;(62):241-52
references.pmid: 12456067
references.citation: Neurosci Lett. 2004 Sep 9;367(3):379-83
references.pmid: 15337270
references.citation: Neurosci Lett. 2005 May 13;379(3):229-34
references.pmid: 15843069
references.citation: Proc Natl Acad Sci U S A. 1995 Nov 21;92(24):11110-4
references.pmid: 7479947
references.citation: Dement Geriatr Cogn Disord. 2006;21(3):139-43
references.pmid: 16391475
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2006 Jun 5;141B(4):387-93
references.pmid: 16649215
references.citation: Mol Psychiatry. 2002;7(2):136-7
references.pmid: 11840305
references.citation: Neuropsychobiology. 2007;55(3-4):151-5
references.pmid: 17657167
references.citation: Nat Genet. 2007 Feb;39(2):168-77
references.pmid: 17220890
references.citation: Int J Neurosci. 2013 Jun;123(6):409-16
references.pmid: 23270505
references.citation: J Neurol. 2005 Apr;252(4):423-8
references.pmid: 15726264
references.citation: Dement Geriatr Cogn Disord. 2006;22(3):216-22
references.pmid: 16899999
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2010 Jan 5;153B(1):235-42
references.pmid: 19504537
references.citation: Cell. 2003 Jan 24;112(2):257-69
references.pmid: 12553913
references.citation: Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6439-43
references.pmid: 8341652
references.citation: J Mol Neurosci. 2004;22(3):257-60
references.pmid: 14997020
references.citation: Neurosci Res. 2006 Jul;55(3):334-41
references.pmid: 16698101