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 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.
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'spatients 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'sAPOE 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: Stacey B Gabriel; Stephen F Schaffner; Huy Nguyen; Jamie M Moore; Jessica Roy; Brendan Blumenstiel; John Higgins; Matthew DeFelice; Amy Lochner; Maura Faggart; Shau Neen Liu-Cordero; Charles Rotimi; Adebowale Adeyemo; Richard Cooper; Ryk Ward; Eric S Lander; Mark J Daly; David Altshuler Journal: Science Date: 2002-05-23 Impact factor: 47.728
Authors: Ahmad R Hariri; Terry E Goldberg; Venkata S Mattay; Bhaskar S Kolachana; Joseph H Callicott; Michael F Egan; Daniel R Weinberger Journal: J Neurosci Date: 2003-07-30 Impact factor: 6.167
Authors: Michael F Egan; Masami Kojima; Joseph H Callicott; Terry E Goldberg; Bhaskar S Kolachana; Alessandro Bertolino; Eugene Zaitsev; Bert Gold; David Goldman; Michael Dean; Bai Lu; Daniel R Weinberger Journal: Cell Date: 2003-01-24 Impact factor: 41.582
Authors: Agnes L Nishimura; João R M Oliveira; Miguel Mitne-Neto; Camila Guindalini; Ricar Nitrini; Valéria S Bahia; Paulo R de Brito-Marques; Paulo A Otto; Mayana Zatz Journal: J Mol Neurosci Date: 2004 Impact factor: 3.444
Authors: Zhe-Yu Chen; Paresh D Patel; Gayatree Sant; Chui-Xiang Meng; Kenneth K Teng; Barbara L Hempstead; Francis S Lee Journal: J Neurosci Date: 2004-05-05 Impact factor: 6.167