Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington's disease
Brain-derived neurotrophic factor does not influence age at neurologic onset of Huntington's disease
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DOI：
10.1016/j.nbd.2006.07.008
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发表时间：
2006-11-01
影响因子：
6.1
通讯作者：
Gusella, James F.
中科院分区：
文献类型：
--
作者：
Kishikawa, Shotaro;Li, Jian-Liang;Gusella, James F.
在亨廷顿病（HD）中，除了HD CAG重复突变外，遗传因素在确定神经系统发病年龄方面也起重要作用。脑源性神经营养因子（BDNF）是纹状体神经元的一种存活因子，被认为是亨廷顿蛋白调控的靶点，是一种有吸引力的遗传修饰剂。我们通过对已知改变BDNF功能的SNP进行基因分型来验证这一假设（rs6265，也称为Va166NIet）和与阿尔茨海默病相关的SNP（BDNF C270 T），沿着两个BDNF内含子SNP（rs7103411，rs11030104），在228例极年轻发作的ED和329例极老年发作的ED中，任何SNP的等位基因频率或基因型频率在组间均未观察到差异。此外，在控制HD重复序列大小的GEE模型或这些SNP的单倍型分析中，未观察到与发病年龄的关联。这些结果表明，BDNF并没有显着影响艾德发病机制，导致神经系统发作。(c)2006爱思唯尔公司All rights reserved.
In Huntington's disease (HD), genetic factors in addition to the HD CAG repeat mutation play a significant role in determining age at neurologic onset. Brain-derived neurotrophic factor (BDNF), a survival factor for striatal neurons, has been implicated as a target of regulation by huntingtin and is an attractive candidate as a genetic modifier. We tested this hypothesis by genotyping a SNP known to alter BDNF function (rs6265, also termed Va166NIet) and a SNP associated with Alzheimer disease (BDNF C270T), along with two BDNF intronic SNPs (rs7103411, rs11030104), in 228 cases with extreme young onset and 329 cases with extreme old onset of ED. No differences were seen between groups for allele frequencies or genotype frequencies for any SNP. Furthermore, no association to onset age was seen in GEE models controlling for HD repeat size or in haplotype analyses of these SNPs. These results indicate that BDNF does not influence significantly the mechanisms in ED pathogenesis that lead to neurologic onset. (c) 2006 Elsevier Inc. All rights reserved.