Dosage Effects of BDNF Val66Met Polymorphism on Cortical Surface Area and Functional Connectivity
Dosage Effects of BDNF Val66Met Polymorphism on Cortical Surface Area and Functional Connectivity
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BDNF Val66Met 多态性对皮质表面积和功能连接的剂量影响
DOI：
10.1523/jneurosci.3501-13.2014
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发表时间：
2014-02-12
影响因子：
5.3
通讯作者：
Jiang, Tianzi
中科院分区：
文献类型：
--
作者：
Wang, Chao;Zhang, Yuanchao;Jiang, Tianzi
脑源性神经营养因子（BDNF）中导致第66位密码子上缬氨酸被甲硫氨酸替代（Val66Met）的单核苷酸多态性（SNP）与认知和记忆功能的差异以及多种神经和精神疾病相关。磁共振成像（MRI）研究已经表明，这种基因变异会导致皮质厚度和体积的变化，但Val66Met多态性是否影响健康受试者的皮质表面积仍不清楚。在此，我们使用多模态MRI研究这种多态性是否会影响大量健康汉族人类受试者的皮质形态和静息态功能连接。基于SNP的一般线性模型分析揭示了甲硫氨酸（Met）等位基因的“剂量效应”，即随着Met等位基因数量的增加，右侧前岛叶皮质的表面积逐步增加。此外，我们发现前岛叶和背外侧前额叶皮质之间的功能连接增强，这与Met等位基因的剂量有关。总之，这些数据表明BDNF Val66Met对正常皮质结构和功能存在“剂量效应”，为探索基因型对认知影响的潜在机制提供了新的途径。
The single nucleotide polymorphism (SNP) that leads to a valine-to-methionine substitution at codon 66 (Val66Met) in BDNF is correlated with differences in cognitive and memory functions, as well as with several neurological and psychiatric disorders. MRI studies have already shown that this genetic variant contributes to changes in cortical thickness and volume, but whether the Val66Met polymorphism affects the cortical surface area of healthy subjects remains unclear. Here, we used multimodal MRI to study whether this polymorphism would affect the cortical morphology and resting-state functional connectivity of a large sample of healthy Han Chinese human subjects. An SNP-wise general linear model analysis revealed a "dosage effect" of the Met allele, specifically a stepwise increase in cortical surface area of the right anterior insular cortex with increasing numbers of the Met allele. Moreover, we found enhanced functional connectivity between the anterior insular and the dorsolateral prefrontal cortices that was linked with the dosage of the Met allele. In conclusion, these data demonstrated a "dosage effect" of BDNF Val66Met on normal cortical structure and function, suggesting a new path for exploring the mechanisms underlying the effects of genotype on cognition.