title: Genetic variants in brain-derived neurotrophic factor associated with Alzheimer's disease.
abstract: BACKGROUND
  Alzheimer's disease is complex, with variants in multiple genes contributing to interactions increasing risk for the disease. Brain-derived neurotrophic factor (BDNF) promotes neuronal survival and modulates hippocampal-dependent memory.
  
  
  METHODS
  We examined 11 SNPs that spanned the gene on chromosome 11p14 in 220 Alzheimer's patients and 128 control spouses.
  
  
  RESULTS
  Not all of the SNPs were informative, due to minor allele frequencies of <2%. Neither C270T nor two SNPs that reside proximal to exon V had significant association with the disease. However, we did find that the heterozygous form of the rs6265 SNP (Val66Met), as well as the diplotype of three SNPs (rs6265, rs11030104, rs2049045; H1-GTC/H2-ACG) all were highly significant in APOE 4 non-carriers (OR = 2.734; p = 0.0096).
  
  
  CONCLUSIONS
  The combination of the diplotypes for three SNPs exhibited significant p values for Alzheimer's APOE 4 non-carriers. The two SNPs (rs11030104 and rs2049045) are found between exons VI and VII, while the Val66Met polymorphism is located in the coding exon VIII; the total distance for the three SNPs is 14308 bp. Whether the SNPs are involved with alternative splicing of the VII/VIII transcript is of considerable interest.
authors.affiliation: Institute of Molecular Medicine and Genetics, Augusta, Georgia, USA.
authors.forename: R
authors.initials: R
authors.lastname: Huang
authors.forename: J
authors.initials: J
authors.lastname: Huang
authors.forename: H
authors.initials: H
authors.lastname: Cathcart
authors.forename: S
authors.initials: S
authors.lastname: Smith
authors.forename: S E
authors.initials: SE
authors.lastname: Poduslo
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D002540:Cerebral Cortex / Q000473:pathology; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012016:Reference Values; D018570:Risk Assessment
chemical_list: D019208:Brain-Derived Neurotrophic Factor