Centre for Brain Aging and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Italy.
J Alzheimers Dis. 2010;22(3):923-31. doi: 10.3233/JAD-2010-101206.
The FOXP2 gene is mutated in a severe monogenic form of speech and language deficits, but no study on the influence of genetic variations within FOXP2 in neurological disorders characterized by language impairment is available yet. In the present study, we investigated the impact of common FOXP2 polymorphisms with regard to frontotemporal lobar degeneration (FTLD). Two-hundred ten FTLD patients underwent clinical and a wide standardized neuropsychological examination as well as brain imaging. In all patients, and in 200 age-matched healthy controls, four FOXP2 polymorphisms were evaluated, namely rs2396753, rs1456031, rs17137124 and rs1852469. SPECT images were analyzed by Statistical Parametric Mapping (SPM5). No significant differences of the four FOXP2 polymorphisms in genotype distribution and allele frequency between FTLD and controls were observed. A significant and specific association between rs1456031 TT and rs17137124 TT genotypes and verbal fluency scores was reported. The two polymorphisms showed an addictive effect. When the analysis was computed on the number of observations over time, and 391 assessments considered, comparable results were obtained. FTLD patients carrying at-risk polymorphisms showed greater hypoperfusion in the frontal areas, namely the left inferior frontal gyrus, and putamen, compared to the non-carriers (p < 0.005). Genetic variations within FOXP2 do not represent a genetic risk to FTLD per se, but modulate FTLD presentation when disease is overt, affecting language performances and leading to hypoperfusion in language-associated brain areas.
FOXP2 基因在严重的单基因言语和语言缺陷中发生突变，但目前尚无研究探讨神经发育障碍中 FOXP2 内遗传变异对语言障碍的影响。本研究旨在探讨常见 FOXP2 多态性对额颞叶变性（FTLD）的影响。210 例 FTLD 患者接受了临床和广泛的标准化神经心理学检查以及脑成像检查。在所有患者和 200 名年龄匹配的健康对照者中，评估了 4 种 FOXP2 多态性，即 rs2396753、rs1456031、rs17137124 和 rs1852469。SPECT 图像由统计参数映射（SPM5）进行分析。未观察到 FTLD 和对照组之间 FOXP2 多态性在基因型分布和等位基因频率上存在显著差异。报告了 rs1456031 TT 和 rs17137124 TT 基因型与言语流畅性评分之间存在显著和特异性关联。两种多态性表现出相加效应。当根据时间观察次数进行分析时，考虑到 391 次评估，得到了可比的结果。与非携带者相比，携带风险多态性的 FTLD 患者的额叶区域，即左侧额下回和壳核，显示出更大的灌注不足（p < 0.005）。FOXP2 内的遗传变异本身并不是 FTLD 的遗传风险因素，但当疾病明显时会影响 FTLD 的表现，影响语言表现并导致与语言相关的大脑区域灌注不足。
