本文選題：精神分裂癥 + GRM3��； 參考：《昆明醫(yī)科大學(xué)》2017年碩士論文

【摘要】：[目的]精神分裂癥是一種復(fù)雜的慢性精神疾病,臨床癥狀多樣,嚴(yán)重威脅人類的身心健康,并且給家庭和社會(huì)帶來沉重負(fù)擔(dān),影響了世界上大約1%的人群,經(jīng)過了一個(gè)多世紀(jì)的研究,其發(fā)病機(jī)制仍不清楚。多年研究發(fā)現(xiàn),精神分裂癥屬多基因遺傳疾病,多個(gè)微效基因的累加效應(yīng)結(jié)合環(huán)境因素共同導(dǎo)致精神分裂癥的發(fā)生,且遺傳因素在精神分裂癥的發(fā)病中起著重要作用,因此易感基因的尋找與確定在精神分裂癥的研究領(lǐng)域中顯得尤為重要。本文從以下兩方面來探索精神分裂癥的易感基因:1.以谷氨酸通路基因?yàn)榍腥朦c(diǎn),探討代謝型谷氨酸受體3基因(Glutamate receptor metabotropic 3,GRM3)和 AMPA 受體 1 基因(AMPA receptor 1,GRIA1)在云南漢族人群中與精神分裂癥的相關(guān)性;2.以全基因組關(guān)聯(lián)數(shù)據(jù)聯(lián)合分析(Genome-wide association study,GWAS)時(shí)篩選出的與感覺門控相關(guān)的轉(zhuǎn)錄因子4基因(Transcription factor 4,TCF4)入手,探討其在云南漢族人群中與精神分裂癥的相關(guān)性。[方法]本研究使用SNaPshot基因分型方法對663例精神分裂癥患者及690例健康對照者中GRM3、GRIA1、TF4 12個(gè)SNPs進(jìn)行基因分型;運(yùn)用Plink 1.07軟件對所選單核苷酸多態(tài)性位點(diǎn)(Single nucleotide polymorphism,SNP)進(jìn)行哈迪溫伯格平衡(Hardy-Weinberg equilibrium,HWE)及相關(guān)性分析;運(yùn)用 Haploview 4.2軟件對同一基因的多態(tài)性位點(diǎn)進(jìn)行連鎖分析;單倍型分析使用SHEsis在線分析軟件(http://analysis.bio-x.cn);多重比較校正采用Bonferroni法;P0.05被認(rèn)為具有統(tǒng)計(jì)學(xué)意義;運(yùn)用在線軟件(http://www.genemania.org/)分析GRM3、GRIA1、TCF4之間是否存在任何功能聯(lián)系;運(yùn)用Quanto 1.2.4軟件對樣本的統(tǒng)計(jì)效能(statisticalpower)進(jìn)行分析。[結(jié)果](1)GRM3、GRIA1單核苷酸多態(tài)性與精神分裂癥的相關(guān)性研究發(fā)現(xiàn)精神分裂癥患者GRIA1多態(tài)性位點(diǎn)rs2926835的T等位基因頻率(P=0.0371)與健康對照相比較差異有統(tǒng)計(jì)學(xué)意義,經(jīng)Bonferroni法校正之后無統(tǒng)計(jì)學(xué)意義(P=0.4083);GRM 多態(tài)性位點(diǎn)rs6465084的A等位基因頻率與對照組相比經(jīng)Bonferroni法校正之后有統(tǒng)計(jì)學(xué)意義(P=0.0273);我們以性別特異性做相關(guān)性分析,發(fā)現(xiàn)多態(tài)性位點(diǎn)rs6465084 A等位基因頻率在女性精神分裂癥患者與正常對照差異顯著(Bonferroni法校正,P=0.0195);其余多態(tài)性位點(diǎn)的等位基因頻率并未發(fā)現(xiàn)與精神分裂癥有關(guān)聯(lián);此外,我們發(fā)現(xiàn)單倍型(A-G)(P=0.004)和(G-G)(P=0.018)在精神分裂癥患者組與健康對照組之間有顯著的統(tǒng)計(jì)學(xué)差異;(2)TCF4單核苷酸多態(tài)性與精神分裂癥的相關(guān)性在本研究中,未發(fā)現(xiàn)TCF4上4個(gè)多態(tài)性位點(diǎn)與精神分裂癥有關(guān)聯(lián)。[結(jié)論]在本研究中,GRM3多態(tài)性位點(diǎn)rs6465084可能與精神分裂癥關(guān)聯(lián),其等位基因A可能增加精神分裂癥的發(fā)病風(fēng)險(xiǎn);rs6465084位點(diǎn)在女性中與精神分裂癥顯著相關(guān),在男性中并無明顯差異;未發(fā)現(xiàn)其余基因的多態(tài)性位點(diǎn)與精神分裂癥有關(guān)聯(lián)。
[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.
【學(xué)位授予單位】：昆明醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R749.3

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本文編號(hào)：1828843