IRCCS National Neurological Institute C. Mondino, Pavia, Italy.
Rejuvenation Res. 2013 Feb;16(1):57-66. doi: 10.1089/rej.2012.1381.
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.
脑源性神经营养因子（BDNF）促进发育过程中神经元的存活，并保护神经元免受各种损伤。BDNF 的产生变化已在不同的神经退行性病理中报道，特别是在阿尔茨海默病（AD）中。我们通过限制性片段长度多态性（RFLP）和实时 PCR 研究了 200 名 AD 患者和 408 名健康对照者的 BDNF Val66Met（G196A）多态性，200 名 AD 患者和 384 名健康对照者的 BDNF 270 C/T 多态性，以及 200 名 AD 患者和 393 名健康对照者的 BDNF 11757 G/C 多态性。我们的结果表明，BDNF 11757 G/C 多态性与 AD 显著相关。在 AD 与健康对照组之间，GG 基因型频率显著增加（p=0.0331），而 CG 基因型频率显著降低（p=0.0194）。我们将注意力集中在单倍型重建上：在 AD 患者与健康对照组之间，TAC 单倍型频率显著降低（p=0.005），CAC 单倍型频率显著增加（p=0.019）。然后，我们根据性别将患者分组，研究单倍型频率。在男性 AD 组中，CAC 单倍型频率显著增加（p=0.041），而在女性 AD 组中，TAC 单倍型频率显著降低（p=0.005），CAC 单倍型频率显著增加（p=0.019）。我们提出，这些单倍型可能是 AD 的另一个有效标志物。
