| 1 | 生物芯片。生物。ACTA 2004年11月1690年：238-49 |
|---|---|
| PMID | 15511631 |
| Title | 大脑表达基因的启动子中的多态性高比例会影响转录活性。 |
| Abstract | There is increasing interest in the possibility that polymorphisms affecting gene expression are responsible for a significant proportion of heritable human phenotypic variation, including human disease. We have sought to determine if polymorphisms in the promoters of brain expressed genes are commonly functional. We screened for polymorphism 56 genes previously reported to be differentially expressed in the brains ofschizophrenics [Y. Hakak, J.R. Walker, C. Li, W.H. Wong, K.L. Davis, J.D. Buxbaum, V. Haroutunian, A.A. Fienberg, Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronicschizophrenia。Proc。纳特。学院科学。98（2001）4746-4751。]。我们发现60种分布在31个基因上的变体。在两个细胞系中的报告基因测定中分析了代表28个不同推定启动子的77个单倍型。在单倍型中代表的总共54个序列变体中，根据高度保守的定义，有12个（或大约22％）起作用。这些是在八个基因的启动子中发现的：NPY，PCSK1，NEFL，KIAA0513，LMO4，HSPA1B, TF and MDH1. We therefore estimate that around 20-25% of promoter polymorphisms in brain expressed genes are functional, and this is likely to be an underestimate. Our data therefore provide for the first time empirical evidence that promoter element polymorphisms, at least in brain expressed genes, should be afforded a high priority for molecular genetic studies. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 2 | 生物芯片。生物。ACTA 2004年11月1690年：238-49 |
| PMID | 15511631 |
| Title | 大脑表达基因的启动子中的多态性高比例会影响转录活性。 |
| Abstract | There is increasing interest in the possibility that polymorphisms affecting gene expression are responsible for a significant proportion of heritable human phenotypic variation, including human disease. We have sought to determine if polymorphisms in the promoters of brain expressed genes are commonly functional. We screened for polymorphism 56 genes previously reported to be differentially expressed in the brains ofschizophrenics [Y. Hakak, J.R. Walker, C. Li, W.H. Wong, K.L. Davis, J.D. Buxbaum, V. Haroutunian, A.A. Fienberg, Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronicschizophrenia。Proc。纳特。学院科学。98（2001）4746-4751。]。我们发现60种分布在31个基因上的变体。在两个细胞系中的报告基因测定中分析了代表28个不同推定启动子的77个单倍型。在单倍型中代表的总共54个序列变体中，根据高度保守的定义，有12个（或大约22％）起作用。这些是在八个基因的启动子中发现的：NPY，PCSK1，NEFL，KIAA0513，LMO4，HSPA1B, TF and MDH1. We therefore estimate that around 20-25% of promoter polymorphisms in brain expressed genes are functional, and this is likely to be an underestimate. Our data therefore provide for the first time empirical evidence that promoter element polymorphisms, at least in brain expressed genes, should be afforded a high priority for molecular genetic studies. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 3 | Neurosci。res。2005年9月53日：8-13 |
| PMID | 15963589 |
| Title | 热休克蛋白70基因（HSPA1A，HSPA1B和HSPA1L）和精神分裂症的多态性。 |
| Abstract | 热休克蛋白70（HSP70）被认为参与schizophrenia关于神经发育。在HSP70中提出了畸变schizophrenia患者，表明它是一个候选基因schizophrenia。This study aimed to investigate the association between the three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L) and HSP70-2 (HSPA1B） 和schizophrenia。One hundred and sixty-one patients withschizophrenia和165个对照组入院。具有限制性片段长度酶（RFLP）的聚合酶链反应（PCR）用于基因型HSPA1A，HSPA1L和HSPA1B多态性。HSPA1A和HSPA1L多态性的等位基因或基因型频率没有显着差异schizophrenia患者和对照组，虽然基因型的频率有边际差异HSPA1B多态性，以及在等位基因的等位基因频率的显着差异HSPA1B多态性之间的多态性schizophrenia患者和对照。没有证据表明临床变量与schizophrenia在三个HSP70基因多态性的基因型中跨越基因型。这些结果表明HSPA1B多态性可能与schizophrenia至少在韩国人口中。因此，应进行来自不同种族的较大研究以确认这些结果。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 4 | 生物。精神病学2007年10月62日：711-21 |
| PMID | 17568569 |
| Title | 精神分裂症前额叶皮质中与免疫和伴侣功能相关的基因表达增加的分子证据。 |
| Abstract | schizophrenia以复杂的基因表达变化为特征。前额叶皮层中的转录组改变已成为最近几项验尸研究的主题，这些研究既产生收敛性和发散发现。 为了提高测量精度，我们使用了具有长寡核苷酸的定制设计的DNA微阵列平台，并具有重复的多个探针。该平台旨在评估特别选择的> 1800个基因的表达，因为它们在病理生理学中的假设作用schizophrenia。来自14对匹配对的背外侧前额叶皮层样品的基因表达差异schizophreniaand control subjects were analyzed with two technical replicates and four data mining approaches. 除了复制许多表达变化in synaptic, oligodendrocyte, and signal transduction genes, we uncovered and validated a robust immune/chaperone transcript upregulation in theschizophreniasamples. 我们推测SERPINA3，IFITM1，IFITM2，IFITM3，CHI3L1，MT2A，CD14，HSPB1，HSPB1，HSPA1B, and HSPA1A inschizophreniasubjects represents a long-lasting and correlated signature of an early environmental insult during development that actively contributes to the pathophysiology of prefrontal dysfunction. |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 5 | Eur Arch Psychiatry Clin Neurosci 2008 Jun 258：239-44 |
| PMID | 18299791 |
| Title | 热休克蛋白70基因多态性在精神分裂症中的关联分析。 |
| Abstract | 热休克蛋白（HSP）是一个有前途的候选基因schizophrenia因为他们被认为在中枢神经系统中起保护作用。对HSP抗体的滴度的改变schizophreniapatients has been suggested. Association between the three polymorphisms of HSP70-1 (HSPA1A), HSP70-hom (HSPA1L) and HSP70-2 (HSPA1B） 和schizophreniahas been reported. Therefore, this study investigated the association between an enlarged set of SNPs at HSP70 gene andschizophrenia。 294例患者schizophreniaand 287 controls were enrolled in the study. Genotypings of 5 SNPs of HSP70 were performed using pyrosequencing method. Haploview 3.2 was used to generate a linkage disequilibrium map and to test for Hardy-Weinberg equilibrium. Single locus and haplotype-based associations were tested. Tests for associations using and multi-marker haplotypes were performed by using a COCAPHASE v2.403. Association of SNP markers and clinical variables were analyzed by analysis of variance. 在RS2075799（等位基因A，X2 = 8.03，DF = 1，P = 0.0046）中检测到显着关联，但在RS2227956（p = 0.28），RS1043618（P = 0.88），RS562047（P = 0.47）（P = 0.47）或RS5396689（P = 0.88）（P = 0.88）（P = 0.28）（P = 0.28）（P = 0.88）（P = 0.88）（P = 0.88）（p = 0.88）（= 0.32）。实际上，RS2075799*g/A基因型在患有schizophrenia比在控件(X2 = 8.23, df = 1, P = 0.0041)。Haplotype based associations were also detected (global P value 0.000003); the T-A-C-C-G haplotype was more prevalent among the patients (odds ratio, OR 5.95). Sliding windows analysis revealed a major contribution from rs2227956 and rs2075799 (global-P value 0.0075), with T-A haplotype significantly associated withschizophrenia。没有证据表明临床变量与schizophrenia跨基因型。 我们的结果提出了HSP70基因（即，RS2075799的单倍型）的可能性可能与发展有关schizophrenia，尽管受到这种疾病的罕见单倍型关联的限制。因此，应进行来自不同种族的进一步研究以确认这些结果。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 6 | Neuropsychobiology 2009 -1 59：135-41 |
| PMID | 19439993 |
| Title | 热休克蛋白70基因变异对精神分裂症住院患者的临床表现和结果的影响。 |
| Abstract | 我们先前研究了一组编码热休克蛋白的基因的单核苷酸多态性（HSPA1A，，，HSPA1B和hspa1l），发现一个HSPA1B变化和schizophrenia(SZ). We now report an association between a set of variations (rs2227956, rs2075799, rs1043618, rs562047 and rs539689) within the same genes and a larger sample ofschizophrenic住院患者。单个变化，RS539689（HSPA1B）发现出院时的正综合征和阴性综合征量表（PANSS）略有相关，单倍型分析显示，与A-C-G-G-G-G-G-G-G-G-G-G单倍型的PANSS得分的改善之间存在显着关联。这些发现进一步支持热休克蛋白在SZ的病理生理中的作用。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 7 | Schizophr Bull 2009 11月35日：1163-82 |
| PMID | 18552348 |
| Title | Schizophrenia susceptibility genes directly implicated in the life cycles of pathogens: cytomegalovirus, influenza, herpes simplex, rubella, and Toxoplasma gondii. |
| Abstract | 许多基因涉及schizophrenia可以与谷氨酸能传播和神经塑性，少突胶质细胞功能以及其他与神经生物学和神经生物学和其他家庭有关schizophrenia表型。其他人似乎似乎参与了与该疾病有关的病原体的生命周期。例如，天冬氨酸葡萄糖苷酶（AGA），PLA2，SIAT8B，GALNT7或B3GAT1代谢化学配体与流感病毒，单纯疱疹，巨细胞病毒（CMV），Rubella，Rubella，Rubella，或Toxoplasma Gondii结合到这些化学配体。CMV使用表皮生长因子受体（EGR/EGFR）进入细胞，并且CMV基因代码用于白介素（IL-10）模拟于结合宿主同源受体IL10R的模拟物。单纯疱疹使用成纤维细胞生长因子受体（FGFR1）。KPNA3和RANBP5控制流感病毒的核进口。破坏了schizophrenia1(DISC1) controls the microtubule network that is used by viruses as a route to the nucleus, while DTNBP1, MUTED, and BLOC1S3 regulate endosomal to lysosomal routing that is also important in viral traffic. Neuregulin 1 activates ERBB receptors releasing a factor, EBP1, known to inhibit the influenza virus transcriptase. Other viral or bacterial components bind to genes or proteins encoded by CALR, FEZ1, FYN,HSPA1B，IL2，HTR2A，KPNA3，MED12，MED15，MICB，NQO2，PAX6，PAX6，PIK3C3，RANBP5或TP53，而单纯疱疹病毒的脑感染性是由Apolipopopopopopopopopopopopopopopopopopopopotion e（APOE）修饰的。与先天性免疫反应相关的蛋白质编码的基因，包括细胞因子相关（CCR5，CSF2RA，CSF2RB，CSF2RB，IL1B，IL1RN，IL2，IL3，IL3，IL3RA，IL4，IL4，IL10，IL10，IL10RA，IL10RA，IL18RAP，IL18RAP，ILYMPHOTOXIN-PHOTOXIN-PHOROSN-PHOROR NECOR NECRAST ALPHASTA [TMOR PHARPHAST IFTAR INPHASTIST FILASTIS FINTH INPHASTIST IFTARSIST INPH CRAPTIST IFTARSIST IFASS IFTAS COSTIS），人白细胞抗原（HLA）抗原（HLA-A10，HLA-B，HLA-DRB1）以及参与抗原加工的基因（血管紧张素转化酶和三肽基肽酶2）均涉及抗抗抗击病原体的防御病原体的抗原。人类microRNA（HSA-MIR-198和HSA-MIR-206）被预测与流感，风疹或脊髓灰质炎病毒基因结合。与某些相关的基因schizophrenia, including those also concerned with neurophysiology, are intimately related to the life cycles of the pathogens implicated in the disease. Several genes may affect pathogen virulence, while the pathogens in turn may affect genes and processes relevant to the neurophysiology ofschizophrenia。对于此类基因，遗传研究中的关联强度可能是由病原体的存在来调节的，病原体在不同时间在不同人群中有所不同，这可能解释了困扰着这种研究的异质性。这种情况还表明，旨在消除与如此清晰相互作用的病原体的药物或疫苗schizophrenia易感基因可能会对疾病的发生产生巨大影响。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 8 | Neuropsychobiology 2009 -1 59：135-41 |
| PMID | 19439993 |
| Title | 热休克蛋白70基因变异对精神分裂症住院患者的临床表现和结果的影响。 |
| Abstract | 我们先前研究了一组编码热休克蛋白的基因的单核苷酸多态性（HSPA1A，，，HSPA1B和hspa1l），发现一个HSPA1B变化和schizophrenia(SZ). We now report an association between a set of variations (rs2227956, rs2075799, rs1043618, rs562047 and rs539689) within the same genes and a larger sample ofschizophrenic住院患者。单个变化，RS539689（HSPA1B）发现出院时的正综合征和阴性综合征量表（PANSS）略有相关，单倍型分析显示，与A-C-G-G-G-G-G-G-G-G-G-G单倍型的PANSS得分的改善之间存在显着关联。这些发现进一步支持热休克蛋白在SZ的病理生理中的作用。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 9 | Transl Psychiatry 2011 -1 1: e9 |
| PMID | 22832404 |
| Title | 焦虑症的收敛功能基因组学：基因，生物标志物，途径和机制的转化鉴定。 |
| Abstract | 与其他主要的精神疾病（如双相情感障碍）和其他主要的精神疾病相比schizophrenia。The fact that they are more common, diverse and perceived as embedded in normal life may explain this relative oversight. In addition, as for other psychiatric disorders, there are technical challenges related to the identification and validation of candidate genes and peripheral biomarkers. Human studies, particularly genetic ones, are susceptible to the issue of being underpowered, because of genetic heterogeneity, the effect of variable environmental exposure on gene expression, and difficulty of accrual of large, well phenotyped cohorts. Animal model gene expression studies, in a genetically homogeneous and experimentally tractable setting, can avoid artifacts and provide sensitivity of detection. Subsequent translational integration of the animal model datasets with human genetic and gene expression datasets can ensure cross-validatory power and specificity for illness. We have used a pharmacogenomic mouse model (involving treatments with an anxiogenic drug--yohimbine, and an anti-anxiety drug--diazepam) as a discovery engine for identification of anxiety candidate genes as well as potential blood biomarkers. Gene expression changes in key brain regions for anxiety (prefrontal cortex, amygdala and hippocampus) and blood were analyzed using a convergent functional genomics (CFG) approach, which integrates our new data with published human and animal model data, as a translational strategy of cross-matching and prioritizing findings. Our work identifies top candidate genes (such as FOS, GABBR1, NR4A2, DRD1, ADORA2A, QKI, RGS2, PTGDS,HSPA1B，dynll2，cckbr和dbp），脑血生物标志物（例如FOS，QKI和HSPA1B），焦虑症的途径（例如cAMP信号传导）和机制 - 尤其是信号转导和对环境的反应性，对海马的作用显着。总体而言，这项工作补充了我们以前的类似工作（关于双相情绪障碍和schizophrenia）在过去十年中进行。它的结论是我们使用CFG的主要精神障碍域三合会基因组景观的程序化第一次通过映射，并允许我们发现焦虑与这些其他主要的精神疾病之间的重大遗传重叠，特别是与未得到认可的重叠的重叠schizophrenia。我们工作发现的PDE10A，TAC1和其他基因为经常观察到的临床合并症和焦虑与其他主要精神疾病之间的相互依赖性提供了分子基础，并将Schizo-Anxize焦虑视为可能的新病学领域。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |
| 10 | Cell Stress Chaperones 2014 Mar 19: 205-15 |
| PMID | 23893339 |
| Title | Heat shock protein 70 gene polymorphisms are associated with paranoid schizophrenia in the Polish population. |
| Abstract | HSP70 genes have been considered as promisingschizophrenia候选基因基于其在压力条件下在中枢神经系统中的保护作用。在这项研究中，我们分析了HSPA1A +190G/C的潜在影响HSPA1B+1267A/G, and HSPA1L +2437T/C polymorphisms in the susceptibility to paranoidschizophrenia在同质的高加索波兰人口中。此外，我们研究了多态性与该疾病的临床变量的关联。23例偏执狂患者schizophrenia和243个健康对照组参与了研究。使用PCR -RFLP技术对HSPA1A，-1B和-1L基因的多态性进行了基因分型。分析在整个组和根据性别分层的亚组中进行。患者和对照组之间HSPA1A多态性的基因型和等位基因频率存在显着差异。+190cc的基因型和 +190C等位基因在患者中的代表性过高，并显着增加了发展的风险schizophrenia（或？=？3.45和或？=？1.61）。有趣的是，具有 +190cc基因型的女性的这种风险要高于 +190cc基因型的男性（或？=？5.78 vs.或？=？=？2.76）。我们还确定CGT单倍型是一种风险单倍型schizophreniaand demonstrated the effects of HSPA1A andHSPA1B关于心理病理学和发作时代的基因型。我们的研究提供了第一个证据，表明HSPA1A多态性可能会增加发展偏执的风险schizophrenia。在不同人群中进行进一步的独立分析，以评估性别的作用以复制这些结果。 |
| SCZ Keywords | 精神分裂症，精神分裂症，精神分裂症患者 |