DTNBP1基因与精神分裂症

目的:了解DTNBP1基因与精神分裂症的连锁关系.方法:选取DTNBP1基因附近的微卫星标志D6s 289,对81个符合美国精神障碍诊断与统计手册第4版诊断标准的精神分裂症受累同胞对及 家系成员共324个个体作基因分型,其中男166例,女158例,患病同胞对81对162例.对分型资料进行非参数连锁分析和传递不平衡分析.结果:两点非参数分析Lod值为0.697 57(P=0.264 885),传递不平衡分析无阳性发现.结论:未能肯定DTNBP1基因是否为精神分裂症的易感基因之一.     

DTNBP1基因与精神分裂症

本文就DTNBP1基因与精神分裂症的关联作一综述。     

DTNBP1基因与精神分裂症的连锁分析

目的:探讨DTNBP1基因与精神分裂症的连锁关系。方法:收集到2个精神分裂症多发家系共54个个体,其中9个受累个体的血样,选取DTNBP1基因附近4对微卫星标记引物(D6S422、D6S289、D6S276、D6S309),采用两点和多点非参数连锁(NPL)分析和Genohunter 2.1软件对这2个家系进行遗传学分析。结果:D6S276两点NPL值为0.978(P=0.086),多点NPL值为1.033(P=0.069),未达到验证性连锁的阈值。D6S422两点和多点NPL值分别为0.154和0.204(P均>0.05);D6S289两点和多点NPL值分别为0.457和0.685(P均>0.05),D6S309两点和多点NPL值分别为0.221和0.324(P均>0.05)。结论:未能验证DTNBP1基因与精神分裂症的连锁关系,但亦不能排除该基因与精神分裂症的相关性。     

精神分裂症神经发育障碍假说的研究进展

<正>精神分裂症是一种病因复杂的重性精神疾病,目前认为遗传和环境共同起作用导致了精神分裂症,有关本病的发病危险因素以及相关因素包括生物学因素和社会环境因素,就生物学因素而言,诸多研究显示本病是多基因遗传,由若干基因叠加作用所致,而非某一基因作用而致;而目前关于神经免疫和内分泌的研究也涉及多个神经递质和激素,以上     

精神分裂症五羟色胺基因多态性

本文对近年 5 -羟色胺神经递质系统的代谢酶、转运体及受体基因多态性与精神分裂症关系的研究报道进行了综述     

精神分裂症五羟色胺基因多态性

本文对近年5-羟色胺神经递质系统的代谢酶、转运体及受体基因多态性与精神分裂症关系的研究报道进行了综述。     

精神分裂症表观遗传学研究进展

精神分裂症的发病机制复杂,传统遗传学研究一直没有突破性进展,近几年的表观遗传学研究发现基因启动子区的甲基化改变会影响到基因的表达水平,进而造成相关神经递质或神经细胞活性的改变,导致疾病的发生,为精神分裂症研究提供了新的方向。     

多巴胺受体和5-羟色胺受体遗传多态性与精神分裂症

精神分裂症患者存在脑多种神经递质如多巴胺 (ＤＡ)、5 羟色胺 (5 ＨＴ)功能失调 ,与此相关的受体可能与这些失调的机制有关。神经递质受体是多种抗精神病药的作用靶 ,药物通过对其进行拮抗或激动来发挥药理作用。分子研究结果已揭示 ,多种编码这些受体蛋白质的基因表现出多态性 ,这些多态性在许多情况下改变了它们对神经递质和特定药物的敏感性。因此 ,不同的受体基因型可能对疾病的易感性不同 ;对不同的个体使用同一剂量的精神药物 ,其临床效应也可能不同。现将近年来关于ＤＡ受体和 5 ＨＴ受体遗传多态性与精神分裂症关系的研究综述于…     

多巴胺受体在精神分裂症认知受损中的作用研究进展

精神分裂症是重性精神疾病之一,临床症状表现为阳性症状、阴性症状、认知症状、攻击敌意和焦虑、抑郁,其中认知症状被认为是疾病的原发性损害,影响患者社会功能的恢复,目前此症状发生的机制不清,研究范围涉及各种神经递质、激素、免疫等方面,现就神经递质多巴胺的受体在精神分裂症认知受损中的作用研究进展进行简要综述,供临床参考.     

墨蝶呤还原酶基因与精神分裂症相关性的研究进展

墨蝶呤还原酶（SPR）催化四氢生物蝶呤（BH4）从头合成途径的最后一步反应。SPR基因遗传缺陷或突变可导致BH。的合成紊乱,影响单胺类神经递质（如多巴胺、5-羟色胺及谷氨酸等）的合成或释放,进而参与包括精神分裂症在内的多种神经精神系统疾病的发生发展过程。此外,SPR基因敲除小鼠表现出持续增强的自主活动等类精神分裂症症状,说明该基因在精神分裂症的发病中扮演重要的角色。进一步研究SPR基因及其单核苷酸多态性的功能,可为阐明精神分裂症的发病机制提供重要的线索,也为新一代抗精神病药物的研制及开发开拓新的视野。现对SPR基因与精神分裂症的相关研究做一综述。     

Is the dysbindin gene (DTNBP1) a susceptibility gene for schizophrenia?

Over recent years the gene DTNBP1 (chromosome 6p24-22) has emerged as one of the most promising candidate genes for schizophrenia. In this article, we review the current genetic evidence that implicates DTNBP1 as a schizophrenia-susceptibility gene. While there is now impressive support from genetic association studies, it is important to remain aware that the actual DTNBP1 susceptibility variants have not been identified. While functional analyses have allowed us to speculate their likely function, only when they are identified will we be able to confidently specify the type of altered gene function that is relevant to schizophrenia pathogenesis. This we hope will then open up new vistas for neurobiological research, allowing us to study the exact contribution of DTNBP1 in schizophrenia, its relationships with various aspects of the phenotype, and the potential of epistatic interactions with other genes, as well as functional interactions between the gene products.     

The role of DTNBP1, NRG1, and AKT1 in the genetics of schizophrenia in Finland

Several putative schizophrenia susceptibility genes have recently been identified. Significant associations between schizophrenia and neuregulin 1 (NRG1) and dysbindin (DTNBP1) were first reported in 2002 and studies in several populations have since independently reported positive associations to these gene regions. Further, both tentative functional and genetic data have implicated the role of AKT1 in the genetic background of this disorder. However, findings have not been consistent in all populations. We investigated the allelic diversity of these three genes NRG1, DTNBP1 and AKT1 in a representative nation-wide study sample of 441 Finnish schizophrenia families consisting of 865 affected individuals, in order to assess their role in one of the largest population-based study samples. DTNBP1 and AKT1 failed to show evidence of association, whereas two SNPs in the 3' region of the NRG1 gene yielded suggestive evidence of association (p=0.012 and p=0.048) in family-based association analyses. Thus, our study does not indicate that AKT1 or DTNBP1 play a role in the etiology of schizophrenia in the Finnish population. Furthermore, results do not support a major role for NRG1, but we cannot completely exclude a minor role of this gene in the Finnish population.     

Mutation analysis of the human dystrobrevin-binding protein 1 gene in schizophrenic patients

Recent molecular genetic studies have reported a positive association of schizophrenia with several single nucleotide polymorphisms (SNPs) and haplotypes from the human dystrobrevin-binding protein 1 (DTNBP1) gene locus on chromosome 6p. This finding suggests that the DTNBP1 gene is likely a susceptible gene for schizophrenia. Because all the SNPs showing positive association with schizophrenia locate at the intronic sequences of the DTNBP1 gene, we set out to search for mutations in the protein-coding sequences and at the 5' promoter region of the DTNBP1 gene to investigate if the DTNBP1 gene is a schizophrenia-susceptible gene. We directly sequenced the cDNA of DTNBP1 gene in 50 schizophrenic patients and the 5' promoter region of the DTNBP1 genomic DNA in 94 schizophrenia patients. No mutations were identified in either the protein-coding sequences or the 5' promoter region of the human DTNBP1 gene in this sample. Thus, in contrast to prior studies reporting positive association of the DTNBP1 gene with schizophrenia in both Irish and German population, our data indicate that the human DTNBP1 is unlikely a major susceptible gene for schizophrenia in Chinese Han patients from Taiwan.     

No association evidence between schizophrenia and dystrobrevin-binding protein 1 (DTNBP1) in Taiwanese families

Several linkage studies have shown significant linkage of schizophrenia to chromosome 6p region, which includes the positional candidate genes, Dystrobrevin-binding protein 1 (DTNBP1). The aim was to examine the association evidence of the candidate gene in 693 Taiwanese families with at least two affected siblings of schizophrenia. We genotyped nine SNPs of this gene with average intermarker distance of 17 kb. Intermarker linkage disequilibrium was calculated with GOLD. Single locus and haplotype association analyses were performed with TRANSMIT program. We found no significant association between schizophrenia and DTNBP1 either through single locus or haplotype analyses. We failed to replicate the association evidence between DTNBP1 and schizophrenia and this gene may not play a major role in the etiology of schizophrenia in this Taiwanese family sample.     

Association of schizophrenia with DTNBP1 but not with DAO, DAOA, NRG1 and RGS4 nor their genetic interaction

Recent reports indicate that DAO, DAOA, DTNBP1, NRG1 and RGS4 are some of the most-replicated genes implicated in susceptibility to schizophrenia. Also, the functions of these genes could converge in a common pathway of glutamate metabolism. The aim of this study was to evaluate if each of these genes, or their interaction, was associated with schizophrenia. A case-control study was conducted in 589 Spanish patients having a diagnosis of schizophrenia, and compared with 617 equivalent control subjects. Several single nucleotide polymorphisms (SNPs) in each gene were determined in all individuals. SNP and haplotype frequencies were compared between cases and controls. The interaction between different SNPs at the same, or at different gene, loci was analyzed by the multifactor dimensionality reduction (MDR) method. We found a new schizophrenia risk and protective haplotypes in intron VII of DTNBP1; one of the most important candidate genes for this disorder, to-date. However, no association was found between DAO, DAOA, NRG1 and RGS4 and schizophrenia. The hypothesis that gene-gene interaction in these five genes could increase the risk for the disorder was not confirmed in the present study. In summary, these results may provide further support for an association between the dysbindin gene (DTNBP1) and schizophrenia, but not between the disease and DAO, DAOA, NRG1 and RGS4 or with the interaction of these genes. In the light of recent data, these results need to be interpreted with caution and future analyses with dense genetic maps are awaited.     

Association between the dysbindin gene (DTNBP1) and cognitive functions in Japanese subjects

Aim:  The dysbindin gene (dystrobrevin binding protein 1: DTNBP1 ) is a susceptibility gene for schizophrenia. Susceptibility genes for schizophrenia have been hypothesized to mediate liability for the disorder at least partly by influencing cognitive performance. This report investigated the relationship between cognitive function and the dysbindin gene.
Methods:  The possible association between a single nucleotide polymorphism (SNP) of DTNBP1 (rs2619539: P1655), which is a risk-independent SNP for schizophrenia in Japanese populations, and memory and IQ was investigated in 70 schizophrenia patients and 165 healthy volunteers in a Japanese population.
Results:  This SNP was associated with two memory scales, verbal memory and general memory, on the Wechsler Memory Scale–Revised (WMS-R), and three subcategories of the Wechsler Adult Intelligence Scale–Revised (WAIS-R), vocabulary, similarities and picture completion in healthy subjects. The SNP, however, did not influence either the indices of WMS-R, IQ or subcategories of WAIS-R in schizophrenia patients.
Conclusion:  A risk-independent SNP in DTNBP1 may have an impact on cognitive functions such as memory and IQ in healthy subjects.     

A genetic variation in the dysbindin gene (DTNBP1) is associated with memory performance in healthy controls

Schizophrenia is a common psychiatric disorder characterized by disturbances of cognition, emotion and social functioning. There are few studies investigating a possible genetic basis for the underlying mechanism of cognitive dysfunctions. A genetic variation in the dysbindin gene (DTNBP1: dystrobrevin binding protein 1), a susceptibility gene for schizophrenia, has been reported to be associated with general cognitive ability and cognitive decline in patients with schizophrenia. Although profound disturbances of memory performance are observed in schizophrenia, only one study has reported a relationship between this gene and spatial working memory in a Caucasian population. We examined a possible association between a protective haplotype of DTNBP1 for developing schizophrenia and memory performance measured by the Wechsler Memory Scale-Revised (WMS-R) and the Wechsler Adult Intelligence Scale-Revised (WAIS-R) in 165 healthy volunteers and 70 patients with schizophrenia in a Japanese population. Healthy controls that carry the protective haplotype showed higher performance in several memory domains measured by the WMS-R than those who did not. Genotype effect on memory performance was not observed in patients with schizophrenia. This haplotype did not affect IQ and its sub-scores as measured by the Wechsler Adult Intelligence Scale-Revised in both groups. These data suggest that DTNBP1 may have impact on parts of memory functions.     

Association study between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia: a meta-analysis

Positional, functional and association studies have strongly implicated the dystrobrevin binding protein 1 gene (DTNBP1) as a promising novel candidate gene for schizophrenia. Since the first association study was reported, there have been many attempts to replicate it. However the results have been mixed and these subsequent studies have produced negative as well as positive results. To reconcile these conflicting findings and to give a comprehensive picture of the relationship of DTNBP1 and schizophrenia, the current meta-analysis combined all published association studies involving nine polymorphisms up to May 2006. The results (12 studies including 3429 cases, 3376 controls and 721 trios) showed that there were five single nucleotide polymorphisms (SNPs) with p values < 0.05, however, sensitivity analyses showed that only one SNP was consistent across all nine studies (four of the five SNPs became non-significant after removal of one study), indicating that one study may cause the association findings for each of these four SNPs. In conclusion, there is only a weak association of one SNP in DTNBP1 with schizophrenia, which is not significant after multiple testing.     

Impact of schizophrenia‐risk gene dysbindin 1 on brain activation in bilateral middle frontal gyrus during a working memory task in healthy individuals

Working memory (WM) dysfunction is a hallmark feature of schizophrenia. Functional imaging studies using WM tasks have documented both prefrontal hypo‐ and hyperactivation in schizophrenia. Schizophrenia is highly heritable, and it is unclear which susceptibility genes modulate WM and its neural correlates. A strong linkage between genetic variants in the dysbindin 1 gene and schizophrenia has been demonstrated. The aim of this study was to investigate the influence of the DTNBP1 schizophrenia susceptibility gene on WM and its neural correlates in healthy individuals. Fifty‐seven right‐handed, healthy male volunteers genotyped for DTNBP1 SNP rs1018381 status were divided in heterozygous risk‐allele carriers (T/C) and homozygous noncarriers (C/C). WM was assessed by a 2‐back vs. 0‐back version of the Continuous Performance Test (CPT), while brain activation was measured with fMRI. DTNBP1 SNP rs1018381 carrier status was determined and correlated with WM performance and brain activation. Despite any differences in behavioral performance, risk‐allele carriers exhibited significantly increased activation of the bilateral middle frontal gyrus (BA 9), a part of the dorsolateral prefrontal cortex (DLPFC), compared to noncarriers. This difference did not correlate with WM performance. The fMRI data provide evidence for an influence of genetic variation in DTNBP1 gene region tagged by SNP rs1018381 on bilateral middle frontal gyrus activation during a WM task. The increased activation in these brain areas may be a consequence of “inefficient” or compensatory DLPFC cognitive control functions. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.