GRIA1、GRM3、TCF4单核苷酸多性与精神分裂症相关性研究

发布时间：2018-05-01 10:03

本文选题：精神分裂症 + GRM3　；参考：《昆明医科大学》2017年硕士论文

【摘要】：[目的]精神分裂症是一种复杂的慢性精神疾病,临床症状多样,严重威胁人类的身心健康,并且给家庭和社会带来沉重负担,影响了世界上大约1%的人群,经过了一个多世纪的研究,其发病机制仍不清楚。多年研究发现,精神分裂症属多基因遗传疾病,多个微效基因的累加效应结合环境因素共同导致精神分裂症的发生,且遗传因素在精神分裂症的发病中起着重要作用,因此易感基因的寻找与确定在精神分裂症的研究领域中显得尤为重要。本文从以下两方面来探索精神分裂症的易感基因:1.以谷氨酸通路基因为切入点,探讨代谢型谷氨酸受体3基因(Glutamate receptor metabotropic 3,GRM3)和 AMPA 受体 1 基因(AMPA receptor 1,GRIA1)在云南汉族人群中与精神分裂症的相关性;2.以全基因组关联数据联合分析(Genome-wide association study,GWAS)时筛选出的与感觉门控相关的转录因子4基因(Transcription factor 4,TCF4)入手,探讨其在云南汉族人群中与精神分裂症的相关性。[方法]本研究使用SNaPshot基因分型方法对663例精神分裂症患者及690例健康对照者中GRM3、GRIA1、TF4 12个SNPs进行基因分型;运用Plink 1.07软件对所选单核苷酸多态性位点(Single nucleotide polymorphism,SNP)进行哈迪温伯格平衡(Hardy-Weinberg equilibrium,HWE)及相关性分析;运用 Haploview 4.2软件对同一基因的多态性位点进行连锁分析;单倍型分析使用SHEsis在线分析软件(http://analysis.bio-x.cn);多重比较校正采用Bonferroni法;P0.05被认为具有统计学意义;运用在线软件(http://www.genemania.org/)分析GRM3、GRIA1、TCF4之间是否存在任何功能联系;运用Quanto 1.2.4软件对样本的统计效能(statisticalpower)进行分析。[结果](1)GRM3、GRIA1单核苷酸多态性与精神分裂症的相关性研究发现精神分裂症患者GRIA1多态性位点rs2926835的T等位基因频率(P=0.0371)与健康对照相比较差异有统计学意义,经Bonferroni法校正之后无统计学意义(P=0.4083);GRM 多态性位点rs6465084的A等位基因频率与对照组相比经Bonferroni法校正之后有统计学意义(P=0.0273);我们以性别特异性做相关性分析,发现多态性位点rs6465084 A等位基因频率在女性精神分裂症患者与正常对照差异显著(Bonferroni法校正,P=0.0195);其余多态性位点的等位基因频率并未发现与精神分裂症有关联;此外,我们发现单倍型(A-G)(P=0.004)和(G-G)(P=0.018)在精神分裂症患者组与健康对照组之间有显著的统计学差异;(2)TCF4单核苷酸多态性与精神分裂症的相关性在本研究中,未发现TCF4上4个多态性位点与精神分裂症有关联。[结论]在本研究中,GRM3多态性位点rs6465084可能与精神分裂症关联,其等位基因A可能增加精神分裂症的发病风险;rs6465084位点在女性中与精神分裂症显著相关,在男性中并无明显差异;未发现其余基因的多态性位点与精神分裂症有关联。
[Abstract]:[objective] schizophrenia is a complex chronic mental disease with multiple clinical symptoms, which seriously threaten the physical and mental health of human beings, and impose a heavy burden on families and society, affecting about 1% of the world's population. After more than a century of research, its pathogenesis is still unclear. Many years of studies have found that schizophrenia is a polygenetic disease, and the cumulative effect of multiple microgenes combined with environmental factors lead to the occurrence of schizophrenia, and genetic factors play an important role in the pathogenesis of schizophrenia. Therefore, the search and identification of susceptibility genes is particularly important in the field of schizophrenia. This paper explores the susceptibility gene: 1 to schizophrenia in the following two ways. To explore the relationship between metabolic glutamate receptor 3 gene Glutamate receptor metabotropic 3 (GRM3) and AMPA receptor 1 gene (AMPA receptor 1pGRIA1) and schizophrenia in Yunnan Han population. Genome-wide association studyGWAS) was used to analyze the transcriptional factor 4 (TCF4) gene associated with sensory gating, and to explore its association with schizophrenia in Yunnan Han population. [methods] SNaPshot genotyping was performed in 663 schizophrenic patients and 690 healthy controls with GRM3-GRIA1TF4 12 SNPs genotyping. The single nucleotide polymorphisms (SNPs) of the selected single nucleotide polymorphisms (SNPs) were analyzed by using Plink 1.07 software, Hardy-Weinberg equilibribrium (HWEE) and Haploview 4.2 were used to analyze the polymorphism loci of the same gene. Haplotype analysis was performed using SHEsis online analysis.bio-x.cnn.Multiple-comparison correction using Bonferroni method (P0.05) was considered to be statistically significant, and the online software http: / www.genemania.orgP was used to analyze whether there was any functional connection between GRM3 and GRIA1TCF4; The statistical power of the sample was analyzed by using Quanto 1.2.4 software. [results] the correlation between single nucleotide polymorphism of GRM3GRIA1 and schizophrenia showed that the T allele frequency of GRIA1 polymorphism locus (rs2926835) in schizophrenic patients was significantly higher than that in healthy controls. There was no statistically significant difference in the A allele frequency of rs6465084 at GRM polymorphism locus 0.4083 by Bonferroni method compared with that of the control group, and compared with that of the control group, the frequency of A allele was significantly higher than that of the control group, and the correlation analysis was made with sex specificity. It was found that the allele frequency of polymorphic locus rs6465084 A was significantly different between female schizophrenic patients and normal controls, and the allele frequencies of other polymorphic loci were not associated with schizophrenia. We found that there was a significant statistical difference between the haplotypes A-GG (0.004) and G-GG (0.018) in schizophrenic patients and healthy controls. There was a significant correlation between TCF4 single nucleotide polymorphisms and schizophrenia in this study. Four polymorphic loci on TCF4 were not found to be associated with schizophrenia. [conclusion] in this study, the polymorphism of GRM3 rs6465084 may be associated with schizophrenia, and allele A may increase the risk of schizophrenia. The rs6465084 locus is significantly associated with schizophrenia in women, but there is no significant difference in men. No polymorphic loci of other genes were found to be associated with schizophrenia.
【学位授予单位】：昆明医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R749.3

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