PDF(Pubmed)
Abstract：
Leucine-rich repeat and immunoglobulin domain-containing protein (Lingo-1) plays a vital role in a large number of neuronal processes underlying learning and memory, which are known to be disrupted in schizophrenia. However, Lingo-1 has never been examined in the context of schizophrenia. The genetic association of a single-nucleotide polymorphism (SNP, rs3144) and methylation (CpG sites) in the Lingo-1 3\'-UTR region was examined, with the testing of cognitive dysfunction and white matter (WM) integrity in a schizophrenia case-control cohort (n = 268/group). A large subset of subjects (97 control and 161 schizophrenia subjects) underwent structural magnetic resonance imaging (MRI) brain scans to assess WM integrity. Frequency of the rs3144 minor allele was overrepresented in the schizophrenia population (p = 0.03), with an odds ratio of 1.39 (95% CI 1.016-1.901). CpG sites surrounding rs3144 were hypermethylated in the control population (p = 0.032) compared to the schizophrenia group. rs3144 genotype was predictive of membership to a subclass of schizophrenia subjects with generalized cognitive deficits (p < 0.05), in addition to having associations with WM integrity (p = 0.018). This is the first study reporting a potential implication of genetic and epigenetic risk factors in Lingo-1 in schizophrenia. Both of these genetic and epigenetic alterations may also have associations with cognitive dysfunction and WM integrity in the context of the schizophrenia pathophysiology.
摘要：
富含亮氨酸的重复序列和含免疫球蛋白结构域的蛋白（Lingo-1）在学习和记忆的大量神经元过程中起着至关重要的作用，已知在精神分裂症中受到干扰。然而,Lingo-1从未在精神分裂症的背景下进行过检查。单核苷酸多态性(SNP，rs3144）和Lingo-13'-UTR区域的甲基化（CpG位点）进行了检查，在精神分裂症病例对照队列（n=268/组）中进行认知功能障碍和白质（WM）完整性测试。大部分受试者（97名对照和161名精神分裂症受试者）接受了结构磁共振成像（MRI）脑部扫描以评估WM完整性。rs3144次要等位基因在精神分裂症人群中的频率过高（p=0.03），比值比为1.39（95%CI1.016-1.901）。与精神分裂症组相比，对照组rs3144周围的CpG位点高度甲基化（p=0.032）。rs3144基因型可预测患有广泛性认知缺陷的精神分裂症受试者的一个亚类的成员（p<0.05），除了与WM完整性相关(p=0.018)。这是第一项研究报告了精神分裂症中Lingo-1遗传和表观遗传风险因素的潜在含义。在精神分裂症病理生理学的背景下，这些遗传和表观遗传改变也可能与认知功能障碍和WM完整性有关。
