Department of Genetics, Faculty in Biology, University of Valencia, C/Doctor Moliner 50, Burjassot, Valencia, Spain.
BMC Med Genet. 2010 Jul 22;11:114. doi: 10.1186/1471-2350-11-114.
Schizophrenia is considered a language related human specific disease. Previous studies have reported evidence of positive selection for schizophrenia-associated genes specific to the human lineage. FOXP2 shows two important features as a convincing candidate gene for schizophrenia vulnerability: FOXP2 is the first gene related to a language disorder, and it has been subject to positive selection in the human lineage.
Twenty-seven SNPs of FOXP2 were genotyped in a cohort of 293 patients with schizophrenia and 340 controls. We analyzed in particular the association with the poverty of speech and the intensity of auditory hallucinations. Potential expansion of three trinucleotide repeats of FOXP2 was also screened in a subsample. Methylation analysis of a CpG island, located in the first exon of the gene, was performed in post-mortem brain samples, as well as qRT-PCR analysis.
A significant association was found between the SNP rs2253478 and the item Poverty of speech of the Manchester scale (p = 0.038 after Bonferroni correction). In patients, we detected higher degree of methylation in the left parahippocampus gyrus than in the right one.
FOXP2 might be involved in the language disorder in patients with schizophrenia. Epigenetic factors might be also implicated in the developing of this disorder.
精神分裂症被认为是一种与语言相关的人类特异性疾病。先前的研究报告了与人类谱系特异性相关的精神分裂症相关基因存在正选择的证据。FOXP2 作为精神分裂症易感性的候选基因，具有两个重要特征：FOXP2 是第一个与语言障碍相关的基因，并且它在人类谱系中经历了正选择。
在一个由 293 名精神分裂症患者和 340 名对照组成的队列中，对 FOXP2 的 27 个 SNP 进行了基因分型。我们特别分析了它们与言语贫乏和听觉幻觉强度的关联。还在亚样本中筛选了 FOXP2 的三个三核苷酸重复的扩展情况。对位于基因第一外显子中的一个 CpG 岛进行了甲基化分析，并进行了 qRT-PCR 分析。
发现 SNP rs2253478 与曼彻斯特量表的言语贫乏项之间存在显著关联（经 Bonferroni 校正后，p = 0.038）。在患者中，我们检测到左侧海马旁回的甲基化程度高于右侧。
FOXP2 可能参与精神分裂症患者的语言障碍。表观遗传因素也可能与这种疾病的发展有关。
