精神分裂症患者中与候选基因相关的候选单核苷酸多态性的关联
Association of Candidate Single Nucleotide Polymorphisms Related to Candidate Genes in Patients With Schizophrenia.
作者信息
Karimian Seyedeh Sara, Akbari Mohammad Taghi, Sadr Seyed Saeed, Javadi Gholamreza
机构信息
Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modarres University, Tehran, Iran.
出版信息
Basic Clin Neurosci. 2020 Sep-Oct;11(5):595-608. doi: 10.32598/bcn.9.10.470. Epub 2020 Sep 1.
INTRODUCTION
Schizophrenia is a chronic heterogenic neurodevelopment disorder. Many genes interfere in the development of SCZ. All four genes, NrCAM, PRODH, ANK3, and ANKK1, which were evaluated in this study, were previously reported to be associated with Schizophrenia. The NrCAM contributes to creating cognitive deficiencies through the CAM's signaling pathway. PRODH plays a vital role in creating SCZ negative symptoms through the signaling pathway of glutamatergic and NMDA receptors. ANK3 affects ion channel and molecular adhesion in Ranvier and initial segments of axons, leading to mental retardation, sleep disorder, and SCZ. ANKK1 encodes a protein kinase and was reported to be associated with alcohol addiction, Attention Deficit Hyperactivity Disorder (ADHD), and SCZ.
METHODS
The subjects were selected from Schizophrenic patients referring to the Psychiatric Ward of Imam-Hussein Hospital and Schizophrenic Patients Support Institution (AHEBBA). 95 (30 Schizoaffective patients, 57 Paranoid patients, and 8 disorganized) patients were recruited as the subjects in the present case-control association study. 120 healthy subjects were recruited from the Tehran Medical Genetics Laboratory staff and a group of students from the Islamic Azad University of Science and Research in Tehran. The genotypes were determined with molecular genotyping techniques of PCR-RFLP, ARMS-PCR, and Cycle sequencing. Results were analyzed by the Chi-Square test using SPSS V. 24 and R, SNP STATE Package to investigate significant differences between cases and controls.
RESULTS
The incidence of schizophrenia was 68% and 32% among men and women, respectively. The evaluation of the allelic association between schizophrenia and all the candidate SNPs showed a significant association between NrCAM's SNP rs10235968 and SCZ (P=0.001). Haplotype T, T, C in rs10235968, rs6967368, rs3763463, respectively, within the NrCAM gene, showed significant association with schizophrenia disorder (P=0.0001).
CONCLUSION
No association was found between other candidate SNPs and SCZ among the subjects.
引言
精神分裂症是一种慢性异质性神经发育障碍。许多基因干扰精神分裂症的发展。本研究中评估的所有四个基因，即NrCAM、PRODH、ANK3和ANKK1，此前均被报道与精神分裂症有关。NrCAM通过细胞粘附分子（CAM）信号通路导致认知缺陷。PRODH通过谷氨酸能和N-甲基-D-天冬氨酸（NMDA）受体信号通路在精神分裂症阴性症状的产生中起重要作用。ANK3影响郎飞结和轴突起始段的离子通道和分子粘附，导致智力迟钝、睡眠障碍和精神分裂症。ANKK1编码一种蛋白激酶，据报道与酒精成瘾、注意力缺陷多动障碍（ADHD）和精神分裂症有关。
方法
研究对象选自侯赛因伊玛目医院精神科病房和精神分裂症患者支持机构（AHEBBA）的精神分裂症患者。在本病例对照关联研究中，招募了95名患者（30名精神分裂症情感障碍患者、57名偏执型患者和8名紊乱型患者）作为研究对象。从德黑兰医学遗传学实验室工作人员和德黑兰伊斯兰阿扎德科学与研究大学的一组学生中招募了120名健康受试者。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）、扩增阻滞突变系统-聚合酶链反应（ARMS-PCR）和循环测序等分子基因分型技术确定基因型。使用SPSS V. 24和R语言的SNP STATE软件包通过卡方检验分析结果，以研究病例组和对照组之间的显著差异。
结果
精神分裂症在男性和女性中的发病率分别为68%和32%。对精神分裂症与所有候选单核苷酸多态性（SNP）之间的等位基因关联进行评估，结果显示NrCAM的SNP rs10235968与精神分裂症之间存在显著关联（P = 0.001）。NrCAM基因内rs10235968、rs6967368、rs3763463的单倍型T、T、C分别与精神分裂症障碍存在显著关联（P = 0.0001）。
结论
在研究对象中，未发现其他候选SNP与精神分裂症之间存在关联。
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