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。     

DTNBP1基因多态性与精神分裂症的研究进展

精神分裂症是以严重的精神障碍为特征的复杂疾病之一,发病机制尚未明确.研究表明该病由多个微效基因与环境因素共同作用导致,遗传因素发挥更至关重要的作用.DTNBP1基因作为精神分裂症的易感基因之一,对谷氨酸、多巴胺等神经递质具有调控作用,与神经递质假说密切相关.目前,国内外已广泛研究DTNBP1基因单核苷酸多态性与精神分裂...     

肿瘤坏死因子基因与精神分裂症的传递不平衡研究

目的 探讨肿瘤坏死因子-α(TNF-α)基因和肿瘤坏死因子-β(TNF-β)基因与精神分裂症的关系.方法 收集172个广东潮汕地区的精神分裂症核心家系,将172例精神分裂症患者分为偏执型(96例)和非偏执型(76例),用聚合酶链反应-限制性片段长度多态性方法 ,检测所有研究对象的TNF-α的3个多态性位点(-C863A、-G308A、-G238A)和TNF-β+A252G位点的等位基因频率和基因型频率,并进行传递不平衡检验(TDT).结果 (1)单位点TDT检验,TNF-β+A252G位点杂合子父母过多地传递等位基因G给患者(X2=5.49,Pc＜0.05),而TNF-α的3个多态性位点(-C863A、-G308A、-G238A)均未发现传递不平衡.(2)多位点联合进行单体型分析,未显示在精神分裂症核心家系中存在传递不平衡;但在96个偏执型精神分裂症核心家系中,有一种常见单体型[(-863C,-308G,-238G,+252G);X2=7.20,Pc＜0.05]存在偏向传递.结论 在广东潮汕人群中,TNF-α和TNF-β基因与精神分裂症可能存在某些关联,该基因可能是偏执型精神分裂症的易感基因.     

隐花色素-1基因与精神分裂症核心家系的传递不平衡分析

目的探讨精神分裂症与隐花色素-1（Cryl）基因多态性的关联关系。方法应用聚合酶链反应和限制性片段长度多态性技术对100个精神分裂症核心家系的Cryl基因上的多态性位点rs2300448、rs1921135和rs1056560进行多态性检测；用Genehunter2．1软件包进行传递不平衡分析（TDT），并构建可能的单体型。结果（1）rs2300448多态性位点等位基因G和等位基因A传递给患病子女的频率差异有统计学意义，等位基因G优先传递给患病子女（X^2=4．92，P=0．027），但P值经Bonferroni校正后，差异无统计学意义（Pc=0．054）；rs1056560和rs1921135多态性位点未发现传递不平衡现象（X^2=0．15，P=0．698；X^2=0．56，P=0．456）。（2）单体型rs2300448-rs1056560G—A（X^2=6．76，P=0．009）、rs1921135-rs2300448-rs1056560T—G—C（X^2=4．50，P=0．034）和C—G—A（X^2=6．37，P=0．012）存在传递不平衡现象，但P值经Bonferroni校正后，T—G—C和C—G—A差异均无统计学意义（Pc〉0．05），只有单体型rs2300448-rs1056560G—A差异有统计学意义（Pc=0．036）。结论Cry1基因可能与精神分裂症相关联。     

精神分裂症和心境障碍混合家系MLC1基因多态性的关联研究

目的在中国汉族人群精神分裂症和心境障碍混合家系中探讨位于22q13的MLC1基因多态性(rs11568171、rs2076137及rs2235349)与精神分裂症、心境障碍的关系。方法在有精神分裂症和心境障碍混合遗传家族史的67个核心家系(包括44个完整的核心家系)中,采用聚合酶链式反应和限制性片断长度多态性(PCR-RFLP)方法,分析MLC1基因上述多态性的基因型及其单体型,进行传递不平衡检验(TDT)。结果患者组与父母组之间,MLC1基因rs11568171T/C、rs2076137T/C及rs2235349T/C多态性等位基因和基因型分布差异无统计学意义(P>0.05),且TDT结果示各多态性在精神分裂症或心境障碍组中父母与患者之间等位基因传递差异均无统计学意义(P>0.05)。单体型TDT显示,精神分裂症患者组中父母与患者之间单体型T-C-T明显传递过少(2=5.0,P<0.05),而单体型C-C-C明显传递过多(2=5.0,P<0.05)。结论在中国汉族人群中MLC1基因可能是精神分裂症的易感基因,但可能不是心境障碍的易感基因。     

早发性精神分裂症核心家系的亚甲基四氢叶酸还原酶基因传递不平衡研究

目的:在中国汉族早发性精神分裂症家系中探讨亚甲基四氢叶酸还原酶(MTHFR)基因与精神分裂症的相关性。方法:采用聚合酶链反应-限制性片段长度多态性方法(PCR-RFLP)技术,检验111个早发性精神分裂症核心家系MTHFR基因A1298C和C677T多态性,并进行连锁不平衡检验(LD)以及传递不平衡检验(TDT)。结果:A1298C及C677T等位基因在父母与先证者间传递差异均无统计学意义(χ2=0.216,P=0.642;χ2=0.143;P=0.706);连锁不平衡检验表明A1298C与C677T之间存在中度连锁不平衡(D'=0.529);单体型TDT显示早发性精神分裂症核心家系中各单体型传递差异均无统计学意义(P>0.05)。结论:MTHFR基因A1298C及C677T多态性与早发性精神分裂症无明显关联。     

Neuregulin-1基因与精神分裂症

nrg-1基因定位于8p2．1-p1．2,它编码的NRG-1蛋白属于表皮生长因子相关蛋白家族,通过与体内受体型酪氨酸蛋白激酶（ErbB）结合,对神经元存活、发育、迁移及髓鞘形成、突触可塑性及功能行使有重要作用,且与谷氨酸能神经元、多巴胺能神经元及GABA能神经元功能密切联系,成为研究精神分裂症重要且有希望的候选基因。     

儿童失神癫癎中基因传递不平衡的初步研究

目的：研究中国北方人群儿童失神癫痫相关基因附近是否存在CAE易患基因位点，或与其存在连锁不平衡。方法：选择8q24位点附的三个微卫星标记物D8S1717、D8S274及D8S1783，在中国北方人群儿童失神癫痫91个核心家系进行传递不平衡检验（TDT）。结果：对D8S274而言，44个含有等位基因A4的父母向患病子女传递了15个A4基因，29个未传递A4基因，X^2＝4．46，P＜0．05，对D8S1783而言，含有等基因A3的父母向患病子女传递了2个A基因，11个未传递A3基因，X^2＝6．23，P＜0．05）。结论：TDT提示染色体8q24附近可能存在CAE易患基因位点，或与其存在连锁不平衡。     

精神分裂症遗传学研究进展

精神分裂症是一种复杂的由多种因素所致的精神障碍，其特征是思维、情感与行为的相互分裂。家系调查、双生子及寄养子研究均支持遗传因素与发病有关。近年来发现人类染色体上一些区域和基因与精神分裂症的发生有关。     

Strong evidence for association between the dystrobrevin binding protein 1 gene (DTNBP1) and schizophrenia in 488 parent-offspring trios from Bulgaria.

BACKGROUND: The gene encoding the dystrobrevin binding protein (DTNBP1) has been implicated in the pathogenesis of schizophrenia by several association studies. We tried to replicate these findings in a sample of 488 parent-proband trios recruited in Bulgaria. Probands had a diagnosis of schizophrenia (n = 441) or schizoaffective disorder (n = 47). METHODS: We genotyped eight single nucleotide polymorphisms within the gene, four of which had been reported in previous studies, and four identified as informative by our group through direct screening of the gene and genotyping in a sample of cases and control subjects. RESULTS: A significant excess of transmissions was observed for two of the markers, p1635 and p1757, (p =.0009 and.0013, respectively). Analysis of two-, three-, and four-marker haplotypes produced numerous positive results, with six (4% of the total combinations) at p <.001. CONCLUSIONS: These results provide strong support for DTNBP1 as a susceptibility gene for schizophrenia; however, different haplotypes seem to be associated in different studies.     

No evidence for association of the dysbindin gene [DTNBP1] with schizophrenia in an Irish population-based study

A recent family-based association study identified a putative association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. This study used a sample of 270 Irish pedigrees multiply affected with schizophrenia. We attempted to replicate these findings in an independent Irish sample of 219 schizophrenia cases and 231 controls. No evidence was found to suggest an association between the DTNBP1 gene and schizophrenia in our sample. Possible reasons for these findings are discussed.     

Untranslated region haplotype in dysbindin gene: analysis in schizophrenia

Summary. Genome-scans performed in schizophrenia families have provided evidence for region 6p24-21 where variability may confer susceptibility to schizophrenia. Recent studies have implicated that gene DTNBP1 (dysbindin) in this region is strongly associated with schizophrenia. In a family based association study we investigated three markers located in the untranslated region of the DTNBP1 gene: rs909706, rs1047631 and rs742106. The sample size of our study is 117 families. No biased transmission towards the disorder was detected by haplotype analysis using TRANSMIT.     

Association study of a functional promoter polymorphism of the X-box binding protein 1 gene in Japanese patients with schizophrenia

The functional promoter polymorphism -116C/G of the X-box binding protein 1 (XBP1) gene was found to be associated with schizophrenia in Han Chinese and Japanese subjects, although contradictive negative findings were also reported in European populations. To confirm this association in a Japanese population, the authors conducted a case-control association study. There was no significant difference in both genotype and allele frequencies between the patients and control subjects, suggesting that the XBP1 -116C/G polymorphism might not confer increased susceptibility for schizophrenia in a Japanese population. However, further studies using a larger sample with detailed clinical data should be performed in several populations.     

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.     

Bipolar disorder and polymorphisms in the dysbindin gene (DTNBP1).

BACKGROUND: Several studies support the dysbindin (dystrobrevin binding protein 1) gene (DTNBP1) as a susceptibility gene for schizophrenia. We previously reported that variation at a specific 3-locus haplotype influences susceptibility to schizophrenia in a large United Kingdom (UK) Caucasian case-control sample. METHODS: Using similar methodology to our schizophrenia study, we have investigated this same 3-locus haplotype in a large, well-characterized bipolar sample (726 Caucasian UK DSM-IV bipolar I patients; 1407 ethnically matched controls). RESULTS: No significant differences were found in the distribution of the 3-locus haplotype in the full sample. Within the subset of bipolar I cases with predominantly psychotic episodes of mood disturbance (n = 133) we found nominally significant support for association at this haploptype (p < .042) and at SNP rs2619538 (p = .003), with a pattern of findings similar to that in our schizophrenia sample. This finding was not significant after correction for multiple testing. CONCLUSIONS: Our data suggest that variation at the polymorphisms examined does not make a major contribution to susceptibility to bipolar disorder in general. They are consistent with the possibility that DTNBP1 influences susceptibility to a subset of bipolar disorder cases with psychosis. However, our subset sample is small and the hypothesis requires testing in independent, adequately powered samples.     

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.