Genetic variants in brain-derived neurotrophic factor associated with Alzheimer's disease

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). Conclusion: The combination of the diplotypes for three SNPs exhibited significant p values for Alzheimer's APOE 4 noncarriers. 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.