Department of Pathology, Dunedin School of Medicine, University of Otago, Dunedin, New Zealand.
Bipolar Disord. 2011 Nov-Dec;13(7-8):630-7. doi: 10.1111/j.1399-5618.2011.00955.x.
Brain-derived neurotrophic factor (BDNF) has important roles in neural cell growth and differentiation. Despite multiple lines of evidence suggesting BDNF as a possible contributor to the pathogenesis of bipolar disorder (BD), the results of genetic association studies have been mixed. We hypothesize that BDNF gene polymorphisms may confer increased susceptibility to BD.
Using a cohort of multiplex bipolar families, we performed family-based association testing to look for associations between BD and eight single nucleotide polymorphisms (SNPs) from BDNF.
We found associations (p < 0.05) between BD and six of the eight SNPs analysed, including two SNPs not previously investigated in association studies. We were able to replicate associations previously found between BD and the Val66Met polymorphism of BDNF (rs6265) and the SNPs rs1519480 and rs12273363. We also found evidence of an association between rs11030107 and BD that was not found in a previous study.
Our results support the hypothesis that some BDNF gene polymorphisms may be contributing factors in the pathogenesis of BD. Our study also adds to the body of evidence associating the functional Val66Met polymorphism of BDNF with BD.
脑源性神经营养因子（BDNF）在神经细胞的生长和分化中具有重要作用。尽管有多项证据表明 BDNF 可能是双相情感障碍（BD）发病机制的一个潜在因素，但遗传关联研究的结果却喜忧参半。我们假设 BDNF 基因多态性可能使个体易患 BD。
使用多基因双相家庭队列，我们进行了基于家庭的关联测试，以寻找 BDNF 中的 8 个单核苷酸多态性（SNP）与 BD 之间的关联。
我们发现 BD 与分析的 8 个 SNP 中的 6 个存在关联（p<0.05），包括两个以前未在关联研究中调查过的 SNP。我们能够复制先前发现的 BDNF 中 Val66Met 多态性（rs6265）和 SNPs rs1519480 和 rs12273363 与 BD 之间的关联。我们还发现了 rs11030107 与 BD 之间存在关联的证据，而之前的一项研究并未发现这种关联。
我们的结果支持以下假设，即一些 BDNF 基因多态性可能是 BD 发病机制的一个促成因素。我们的研究还增加了将 BDNF 的功能 Val66Met 多态性与 BD 相关联的证据。
