| 1 | Schizophr. Res. 2009 Apr 109: 121-9 |
|---|---|
| PMID | 19232479 |
| 标题 | Does the presenilin 2 gene predispose to schizophrenia? |
| 抽象的 | presenilins是一组蛋白质，在可能与之相关的Notch，ERBB4和Wnt信号通路中起重要作用schizophrenia。PRESENILIN 2的基因编码2（PSEN2) is located on 1q42 and adjacent to a balanced translocation t (1; 11) (q42; q14.3) that was found to co-segregate within family members of patients withschizophrenia。We thus hypothesized thatPSEN2may contribute to the pathogenesis ofschizophrenia。Five functional SNPs (rs1295645, rs11405, rs6759, rs1046240 and rs8383) present in the coding regions of thePSEN2在410例患者中测试了基因schizophrenia在中国汉族人口众多和355名对照n. Association analysis showed a weak association for rs1295645 and the rs1295645-T allele was involved in increased risk ofschizophrenia(corrected p=0.045, OR=1.32, 95% CI 1.04-1.68). The T-C-T-T-T haplotype also showed association with increased risk of the illness (p=1.8x10(-5), OR=3.37, 95% CI 1.33-8.51). Analysis of gene expression demonstrated thatPSEN2mRNA levels in peripheral leukocytes were significantly lower in the patient group than in the control group and that expression levels of thePSEN2基因与其基因型显着相关。临床特征的分析显示PSEN2基因和一些使用PANSS评分的临床表型。目前的结果表明PSEN2gene may be a novel candidate involved in the development of certain psychotic symptoms ofschizophreniaalthough the initial finding needs further replication in a large sample size. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 2 | 是。J. Med。基因。B Neuropsychiatr。基因。2013年3月162B：191-200 |
| PMID | 23335491 |
| 标题 | 精神分裂症中DAOA基因的遗传关联和脑成像的联合研究。 |
| 抽象的 | While there has been no objective biomarker available for both diagnosis and prognosis ofschizophrenia, compelling evidence suggests that the glutamatergic system may influence susceptibility toschizophrenia。To test genetic association of the glutamatergic system withschizophrenia和静止状态患者的脑活动异常schizophrenia，对454例患者和480例对照进行了两阶段的关联研究，然后对48例无蛋白质药物药物和43例匹配的对照组进行了静止状态功能磁共振成像的区域均匀性（REHO）分析。最初，学生的t检验和2�2（基因型 - 疾病状态）ANOVA进行了测试，对感兴趣的基因型之间的REHO之间的差异进行了测试，以识别基因型，疾病状态及其相互作用的主要影响，疾病状态及其相互作用在schizophrenia。The stage-1 study showed association of the DAOA andPSEN2带有基因schizophrenia在一个小样本中；使用扩展样品的2期研究证实了2-SNP和3-SNP单倍型的疾病关联，以及DAOA基因中RS2391191和其他一些SNP之间的顺式相互作用。在双侧库尔曼，左壳和左胸腔中有四个因reho改变的簇与2391191卢比相关。RS2391191基因型的主要作用在左壳核中发现。左CUNEUS显示出基因型 - 疾病状态相互作用。总之，DAOA基因可能赋予schizophrenia并与更改的Reho交往schizophrenia;基因型效应及其与疾病状况的相互作用可能有助于改变REHO，导致特定的REHOschizophrenicbrain due to glutamatergic modulation. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 3 | 是。J. Med。基因。B Neuropsychiatr。基因。2013年3月162B：191-200 |
| PMID | 23335491 |
| 标题 | 精神分裂症中DAOA基因的遗传关联和脑成像的联合研究。 |
| 抽象的 | While there has been no objective biomarker available for both diagnosis and prognosis ofschizophrenia, compelling evidence suggests that the glutamatergic system may influence susceptibility toschizophrenia。To test genetic association of the glutamatergic system withschizophrenia和静止状态患者的脑活动异常schizophrenia，对454例患者和480例对照进行了两阶段的关联研究，然后对48例无蛋白质药物药物和43例匹配的对照组进行了静止状态功能磁共振成像的区域均匀性（REHO）分析。最初，学生的t检验和2�2（基因型 - 疾病状态）ANOVA进行了测试，对感兴趣的基因型之间的REHO之间的差异进行了测试，以识别基因型，疾病状态及其相互作用的主要影响，疾病状态及其相互作用在schizophrenia。The stage-1 study showed association of the DAOA andPSEN2带有基因schizophrenia在一个小样本中；使用扩展样品的2期研究证实了2-SNP和3-SNP单倍型的疾病关联，以及DAOA基因中RS2391191和其他一些SNP之间的顺式相互作用。在双侧库尔曼，左壳和左胸腔中有四个因reho改变的簇与2391191卢比相关。RS2391191基因型的主要作用在左壳核中发现。左CUNEUS显示出基因型 - 疾病状态相互作用。总之，DAOA基因可能赋予schizophrenia并与更改的Reho交往schizophrenia;基因型效应及其与疾病状况的相互作用可能有助于改变REHO，导致特定的REHOschizophrenicbrain due to glutamatergic modulation. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 4 | Neuropsychiatr Dis Treat 2015 -1 11: 2315-22 |
| PMID | 26396515 |
| 标题 | Identification of two novel mutations, PSEN1 E280K and PRNP G127S, in a Malaysian family. |
| 抽象的 | 阿尔茨海默氏病（AD）是痴呆症的最常见形式，可以分为两种主要形式：早期AD和晚期AD。早期AD的遗传背景已被充分了解，三个基因，应用程序，PSEN1和PSEN2have been identified as causative genes. In the current study, we tested three siblings from Malaysia who were diagnosed with early onset dementia, as well as their available family members. The family history was positive as their deceased father was similarly affected. Patients were tested for mutations in APP, PSEN1,PSEN2, and PRNP. A novel variant, E280K, was discovered in exon 8 of PSEN1 in the three siblings. In silico analyses with SIFT, SNAP, and PolyPhen2 prediction tools and three-dimensional modeling were performed, and the results suggested that the mutation is probably a pathogenic variant. Two additional pathogenic mutations were previously been described for codon 280, E280A, and E280G, which could support the importance of the E280 residue in the PS1 protein contributing to the pathogenic nature of E280K. Additional ten family members were screened for the E280K mutation, and all of them were negative. Six of them presented with a variety of neuropsychiatric symptoms, including learning disabilities, epilepsy, andschizophrenia, while four family members were asymptomatic. A novel PRNP G127S mutation was found in a step-niece of the three siblings harboring the PSEN1 E280K mutation. In silico predictions for PRNP G127S mutation suggested that this might be possibly a damaging variant. Additional studies to characterize PRNP G127S would be necessary to further understand the effects of this mutation. |
| SCZ关键字 | 精神分裂症，精神分裂症 |
| 5 | J. Alzheimers Dis. 2016 Mar 52: 581-608 |
| PMID | 27031468 |
| 标题 | The Zebrafish Equivalent of Alzheimer's Disease-Associated PRESENILIN Isoform PS2V Regulates Inflammatory and Other Responses to Hypoxic Stress. |
| 抽象的 | Dominant mutations in the PRESENILIN genes PSEN1 andPSEN2cause familial Alzheimer's disease (fAD) that usually shows onset before 65 years of age. In contrast, genetic variation at the PSEN1 andPSEN2基因座似乎并没有导致疾病的零星，晚期发作形式（SAD）的风险，导致怀疑这些基因在大多数AD病例中起作用。但是，截短的同工型PSEN2, PS2V, is upregulated in sAD brains and is induced by hypoxia and high cholesterol intake. PS2V can increase ?-secretase activity and suppress the unfolded protein response (UPR), but detailed analysis of its function has been hindered by lack of a suitable, genetically manipulable animal model since mice and rats lack this PRESENILIN isoform. We recently showed that zebrafish possess an isoform, PS1IV, that is cognate to human PS2V. Using an antisense morpholino oligonucleotide, we can block specifically the induction of PS1IV that normally occurs under hypoxia. Here, we exploit this ability to identify gene regulatory networks that are modulated by PS1IV. When PS1IV is absent under hypoxia-like conditions, we observe changes in expression of genes controlling inflammation (particularly sAD-associated IL1B and CCR5), vascular development, the UPR, protein synthesis, calcium homeostasis, catecholamine biosynthesis, TOR signaling, and cell proliferation. Our results imply an important role for PS2V in sAD as a component of a pathological mechanism that includes hypoxia/oxidative stress and support investigation of the role of PS2V in other diseases, includingschizophrenia，当这些与病理有关时。 |
| SCZ关键字 | 精神分裂症，精神分裂症 |