Brain-derived neurotrophic factor gene variants and Alzheimer disease: an association study in an Alzheimer disease Italian population.

Brain-derived neurotrophic factor (BDNF) promotes neuronal survival during development and protects neurons from insults of various kinds. Changes in production of BDNF have been reported in differing neurodegenerative pathologies and, in particular, in Alzheimer disease (AD). We studied 200 AD patients and 408 healthy controls for BDNF Val66Met(G196A) polymorphism, 200AD and 384 healthy controls for BDNF 270 C/T polymorphism, and 200AD and 393 healthy controls for BDNF 11757 G/C polymorphism by restriction fragment length polymorphism (RFLP) and real-time PCR. Our results indicated that the 11757 G/C BDNF polymorphism was significantly associated with AD. A statistically significant increase of GG genotype frequency in AD versus healthy subjects (p=0.0331) was observed, whereas the CG genotype demonstrates a statistically significant decrease of frequency in AD patients versus controls (p=0.0194). We focused our attention on haplotype reconstruction: A statistically significant decrease of the TAC haplotype frequency in AD patients versus healthy controls group (p=0.005) and a statistically significant increase of the CAC haplotype frequency in patients versus control (p=0.019) was demonstrated. We then studied the haplotype frequencies dividing patients according to gender. A statistically significant increase of the CAC haplotype in the male AD group compared with male healthy controls (p=0.041) was found, whereas a statistically significant decrease of TAC haplotype frequency in AD females versus healthy females (p=0.005) and a statistically significant increase of CAC haplotype frequency in female patients versus healthy females (p=0.019) was noticed. We propose that these haplotypes could be a further effective marker for AD.