精神分裂症脑源性神经营养因子C270T基因多态性研究

目的 探讨脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)基因C270T多态性与精神分裂症的相关性.方法 用聚合酶链反应技术检测224例精神分裂症和220例正常人的BDNF基因C270T基因型和等位基因,以阳性与阴性症状量表评定患者的临床症状,比较C270T基因型和等位基因分布频率差异及其与精神分裂症临床症状的相关性.结果 患者组的C/T基因型分布频率显著高于对照组(27.7％ vs.6.8％),P＜ 0.01;T等位基因分布频率显著高于对照组(14.7％ vs.3.2％)P＜0.001;BDNF基因C270T的基因型C/C、C/T、T/T分布频率和等位基因C、T的分布频率,阳性组与阴性组比较差异均无统计学意义(均P＞0.05).结论 BDNF基因C270T多态性与精神分裂症相关,但与临床症状不相关.     

脑源性神经营养因子基因单体型与散发性Alzheimer病的关系

目的分析汉族人群中脑源性神经营养因子(BDNF)基因G196A、C270T、G11757C和G712A单核苷酸多态性(SNPs)和单体型频率与散发性Alzheimer病(sAD)的关系。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,检测106例sAD患者和110名健康对照者BDNFG196A、C270T、G11757C和G712A基因型和等位基因频率,采用SHEsis软件进行连锁不平衡及单体型分析。结果sAD组及健康对照组C270T位点T等位基因频率分别为0.9%及4.5%,G712A位点GG基因型频率分别为95.4%、91.8%,A等位基因频率分别为0.5%及4.5%;两组比较差异有统计学意义(均P<0.05)。单体型分析显示,sAD组和健康对照组GTGA频率分别为0.5%和3.2%,差异有统计学意义(P<0.05)。结论BDNF基因多态性可能与中国汉族人群sAD发病有关。     

脑源性神经营养因子基因多态性与散发性帕金森病的相关性研究

目的探讨脑源性神经营养因子(Brain-DerivedNeurotrophicFactor,BDNF)基因多态性与散发性帕金森病(SporadicParkinson'sDisease,SPD)的相关性。方法采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)分析方法对196例健康人和85例SPD患者进行基因分型;利用x2检验统计分析实验数据。结果两组间BDNF基因G196A和C270T多态性位点各基因型和等位基因频率差异均无显著性(P>0.05)。结论BDNF基因多态性与SPD无显著相关性。     

脑源性神经营养因子基因C270T多态性与儿童精神分裂症的关系

目的 探讨脑源性神经营养因子(BDNF)基因C270T多态性与儿童精神分裂症的关系.方法 采用病例对照研究,用聚合酶链反应-限制性片段长度多态性方法,分析204例儿童精神分裂症患者和210名健康对照的BDNF基因C270T多态性;进行阳性与阴性症状量表(PANSS)评定,用Andremson阳性与阴性精神分裂症分型标准将患者分为阴性症状为主型(阴性组)和阳性症状为主型(阳性组).结果 ①患者组和对照组间BDNF基因C270T多态性的基因型频率差异有统计学意义(χ2=24.56,P<0.01),前者的C/T型和T/T型频率高于后者;患者组等位基因T频率显著高于对照组(χ2=24.04,P<0.01);②阴性组、阳性组、对照组3组间基因型及等位基因分布的差异均有统计学义(χ2=37.93,P<0.01;χ2=38.90,P<0.01);两两比较显示,阴性组、阳组分别与对照组比较,基因型及等位基因分布差异均有统计学义(P<0.001).③不同基因型患者组之间PANSS各因子分和总分差异均无统计学意义(P>0.05).结论 BDNF C270T多态性与儿童精神分裂症有关,但与具体临床表现之间无明显的关系.     

脑源性神经营养因子基因C270T多态性与精神分裂症临床表型的关联研究

目的探讨脑源性神经营养因子（BDNF）基因C270T多态性与精神分裂症临床表型的关系。方法对130例身体健康的精神分裂症患者（研究组）及144例正常人（对照组）应用聚合酶链反应、琼脂糖凝胶电泳结合溴乙锭染色技术检测脑源性神经营养因子基因C270T多态性;采用阳性与阴性症状量表（PANSS）评定精神分裂症临床表型。用χ^2检验和单因素方差分析脑源性神经营养因子基因与精神分裂症临床表型的关系。结果两组BDNF基因型分布及等位基因的频率分布差异无统计学意义（P〉0．05）,但是患者组中C／C和C／T两组基因型患者的PANSS阴性分量表得分有显著性差异（P〈0．05）。结论BDNF C270T的基因多态性可能与精神分裂症易感性没有直接关系,但是,BDNF的基因变异可能与精神分裂症的病理症状有关。     

脑源性神经营养因子基因多态性与精神分裂症的关联研究

目的:探讨脑源性神经营养因子(BDNF)基因多态性与精神分裂症的关联性.方法:以111例精神分裂症发作期患者与362例正常对照为研究对象,通过TagMan探针单核苷酸多态性(SNP)基因分型技术对BDNF基因及基因上游10 kb区域的标签SNPs rs6265和rs11030101进行基因分型,比较各组间基因型、等位基...     

脑源性神经营养因子与抑郁症

神经营养因子是神经元网络形成和可塑性的重要调节因子,以脑源性神经营养因子(BDNF)最受关注。抗抑郁治疗通过提高BDNF表达来促进神经元可塑性,从而取得疗效。本文从临床前研究、临床研究和基因多态性等方面对BDNF与抑郁症作一综述。     

抑郁症患者脑源性神经营养因子Va166Met多态性与血清浓度的关系

目的 探讨脑源性神经营养因子(BDNF)基因Va166Met多态性与抑郁症之间的关系以及Va166Met多态性是否影响血清BDNF浓度.方法 对76例未经药物治疗的抑郁症患者和50例正常人,用限制性片段长度多态性方法分析Va166Met多态性,采用酶联吸附反应方法对血清BDNF浓度进行检测.结果 (1)抑郁症患者血清BDNF浓度(24.7±12.7)ng/ml显著低于正常对照组(36.6±16.4)pg/ml,差异有统计学意义(P＜0.01);(2)抑郁症组和对照组之间的Va166Met多态性位点的等位基因频率和基因型分布差异无统计学意义(P＞0.05);(3)在押郁症组和对照组,Val/Met+Met/Met基因型组与Val/Val基因型相比,血清BDNF浓度差异无统计学意义(P＞0.05).结论 抑郁症患者存在较低的血清BDNF水平,BDNF基因Val66Met多态性与抑郁症之间无相关性,Va166Met多态性对血清BDNF水平浓度无明显影响.     

抑郁症患者脑源性神经营养因子Val66Met多态性与血清浓度的关系

目的探讨脑源性神经营养因子（BDNF）基因Val66Met多态性与抑郁症之同的关系以及Val66Met多态性是否影响血清BDNF浓度。方法对76例未经药物治疗的抑郁症患者和50例正常人,用限制性片段长度多态性方法分析Val66Met多态性,采用酶联吸附反应方法对血清BDNF浓度进行检测。结果（1）抑郁症患者血清BDNF浓度（24．7±12．7）ng／m1显著低于正常对照组（36．6±16．4）pg／m｜,差异有统计学意义（P〈0．01）;（2）抑郁症组和对照组之间的Val66Met多态性位点的等位基因频率和基因型分布差异无统计学意义（P〉0．05）;（3）在抑郁症组和对照组,Val／Met＋Met／Met基因型组与Val／Val基因型相比,血清BDNF浓度差异无统计学意义（P〉0．05）。结论抑郁症患者存在较低的血清BDNF水平,BDNF基因Val66Met多态性与抑郁症之间无相关性,Val66Met多态性对血清BDNF水平浓度无明显影响。     

脑源性神经营养因子与亨廷顿病

脑源性神经营养因子(BDNF)支持多种神经元的生存、发育和分化。在基因转录水平,野生型huntingtin和突变型huntingtin有区别地调节BDNF的表达,以及BDNF的轴突转运功能发生障碍,使亨廷顿病患者和模型动物脑内BDNF减少,导致纹状体神经元的丢失。BDNF可以保护纹状体的易感性神经元,但是将BDNF用于治疗HD还存在许多困难。     

Prefrontal cognition in schizophrenia and bipolar illness in relation to Val66Met polymorphism of the brain-derived neurotrophic factor gene

The measures of prefrontal cognition have been used as endophenotype in molecular-genetic studies. Brain-derived neurotrophic factor (BDNF) has been implicated in cognitive functions and in the pathogenesis of major psychoses. This study investigates the relationship between Val66Met polymorphisms of the BDNF gene and prefrontal cognitive function in 129 patients with schizophrenia and 111 patients with bipolar mood disorder. Cognitive tests included the Wisconsin Card Sorting Test (WCST), with such domains as number of perseverative errors, non-perseverative errors, completed corrected categories, conceptual level responses, and set to the first category, and the N-back test, where mean reaction time and percent of correct reactions were measured. Genotyping for Val66Met BDNF polymorphism was done by polymerase chain reaction method. In schizophrenia, no relationship between Val66Met polymorphism of the BDNF gene and the results of the WCST was observed. Patients with Val/Val genotype had a higher percentage of correct reactions in the N-back test than those with the remaining genotypes. Bipolar patients with Val/Val genotype obtained significantly better results on three of five domains of the WCST. No relationship between BDNF polymorphism and the results of the N-back test was found in this group. A limitation to the results could be variable psychopathological state and medication during cognitive testing and lack of Hardy-Weinberg equilibrium in schizophrenia group. Val66Met polymorphism of the BDNF gene may be associated with cognitive performance on the WCST in bipolar mood disorder but not in schizophrenia. An association of this polymorphism with performance on the N-back test in schizophrenia and not in bipolar illness may suggest that in schizophrenia, the BDNF system may be connected with early phases of information processing.     

载脂蛋白E基因多态性与Alzheimer病

目的：探讨广东地区Ａｌｚｈｅｉｍｅｒ病（ＡＤ）患者与ａｐｏＥε４之间的关联性及性别的影响。方法：应用聚合酶链反应－限制性片段长度多态性分析（ＰＣＲ－ＲＦＬＰ）的技术对４４例晚发性散发性ＡＤ患者、３７例非痴呆老年人的ａｐｏＥ基因进行分型。结果：ａｐｏＥε４与晚发性ＡＤ有显著的关联;携带１个或１个以上ε４者与无ε４携带者比较,相对危险度（ＯＲ值）为４．０８,且随ε４基因剂量增加,ＡＤ的患病率上升,发病年龄明显提前（Ｐ＜０．０１）;ＡＤ患者不同性别之间ａｐｏＥε４基因型频率和等位基因频率无显著性差异（Ｐ＞０．０５）。结论ａｐｏＥε４是晚发性ＡＤ发病的危险因素;ＡＤ患者的性别因素与ａｐｏＥε４无相关性。     

Brain-derived neurotrophic factor gene polymorphisms in Japanese patients with sporadic Alzheimer's disease, Parkinson's disease, and multiple system atrophy.

We studied two genetic polymorphisms (240C/T and 480G/A) of the brain-derived neurotrophic factor (BDNF) gene in Japanese patients with Alzheimer's disease (AD, n = 172), Parkinson's disease (PD, n = 327), and multiple system atrophy (MSA, n = 122), as well as controls (n = 275). The distribution of the 240 C/T polymorphism was significantly different between AD patients and controls, whereas there was no difference in the genotype of the two polymorphisms between MSA and controls or between PD and controls. Our data suggest that BDNF might play a role in AD.     

Codon 129 polymorphism of prion protein gene in sporadic Alzheimer's disease

Codon 129 polymorphism of the prion protein gene represents a major genetic risk factor for Creutzfeldt-Jakob disease (CJD). Both CJD and Alzheimer's disease (AD) are brain amyloidoses and it would be possible that codon 129 polymorphism plays a role in the susceptibility to AD. In order to investigate this polymorphism in AD the distribution of polymorphic codon 129 of the PRNP gene in 194 probable AD and 124 controls selected in Italy and 109 neuropathologically verified AD and 58 matched controls recruited in the USA was studied. No significant association was found for the PRNP polymorphism in AD compared to controls either in Probable or in Definite AD series even after stratification for APOE polymorphism. This study does not support a role of PRNP polymorphism as a susceptibility factor for AD.     

脑源性神经营养因子Val66Met功能基因多态性与抗抑郁剂疗效

目的：探讨脑源性神经营养因子（BDNF）Val66Met功能基因多态性与抗抑郁剂临床疗效的相关性。方法：302例抑郁症患者给予抗抑郁剂治疗8周。于治疗前和治疗2、4、6、8周后采用汉密尔顿抑郁量表（HAMD）评定抑郁严重程度和疗效。以治疗后HAMD总分≤7分为临床痊愈,将302例患者分为痊愈组160例和未痊愈组142例,抽取患者静脉血,采用Illumina GoldenGate定制芯片分析BDNFVal66Met基因多态性并进行基因分型。结果：痊愈组基因型分布A/A31例（19.4%）、A/G92例（57.5%）和G/G37例（23.1%）,未痊愈组分别为28例（19.7%）、78例（54.9%）和36例（25.4%）（χ2=0.054,P=0.817）;痊愈组等位基因频率分布A154例（48.1%）和G166例（51.9%）,未痊愈组分别为134例（47.2%）和150例（52.8%）（χ2=0.247,P=0.884）。3种BDNFVal66Met基因型患者间在性别、年龄、受教育年限、病程、发病次数、有无精神疾病家族史、HAMD基线及减分率上差异均无统计学意义（P均〉0.05）。结论：BDNFVal66Met基因多态性不是影响抗抑郁剂治疗近期疗效的主要因素。     

精神分裂症自杀未遂者脑源性神经营养因子研究

目的:探讨影响精神分裂症自杀未遂患者脑源性神经营养因子(BDNF)水平的相关因素。方法:采用横断面病例-对照研究设计。研究包括精神分裂症自杀未遂组20例,精神分裂症无自杀行为组28例,正常对照组30名。采用酶联免疫吸附试验法测定血清BDNF浓度。采用简明精神病评定量表(BPRS)和自杀意图自评量表(SIOSS)对患者组进行评定。比较各组BDNF水平及其与相关因素之间的关系。结果:三组间BDNF水平差异有统计学意义(F=32.395,P<0.01)。Post-hoc分析发现,精神分裂症自杀未遂组BDNF水平[(51.3±11.1)pg/ml]显著低于精神分裂症无自杀行为组[(67.7±20.8)pg/ml](P<0.05),而精神分裂症无自杀行为组BDNF水平也低于正常对照组[(111.3±39.0)pg/ml](P<0.01)。自杀未遂组的血清BDNF水平与自杀严重程度呈负相关(r=-0.836,P<0.01)。结论:精神分裂症自杀未遂患者BDNF水平低于精神分裂症无自杀行为患者和正常人群;BDNF可能是参与精神分裂症自杀病理生理机制的一种重要物质。     

侧脑室内注入脑源性神经营养因子对AD小鼠酪氨酸激酶B及内源性BDNF表达的影响

目的 探讨侧脑室内注入脑源性神经营养因子(BDNF)对APP/PS1双转基因阿尔茨海默病(AD)小鼠酪氨酸激酶B (TrkB)及内源性BDNF表达的影响. 方法 10只10月龄APP/PS1雄性小鼠按随机数字表法分为2组,实验组5只,双侧侧脑室内注入BDNF;磷酸盐缓冲液(PBS)组5只,双侧侧脑室内注入PBS,为阳性对照组;干预时间均为6周.同时选择5只同窝生10月龄野生型小鼠,不予任何处理,为阴性对照组.采用荧光免疫组化法观察小鼠皮层区β-淀粉样蛋白(Aβ)斑块形态学改变,硫磺素S法检测致密斑的数量,同时检测小鼠皮层区TrkB、BDNF蛋白表达的情况. 结果 (1)治疗前、后BDNF组Aβ斑块总数分别为(101.58±7.86)个、(102.83±8.22)个,与PBS组(97.23±1 1.62)个、(103.6±6.46)个比较差异均无统计学意义(t=0.695、-0.171,P=-0.509、0.869);治疗6周后BDNF组Aβ斑块直径缩小至(34.65±9.33)μm,TS+斑块数量减少至(51.70±4.18)个,与PBS组(46.17±10.16)μm、(58.85±7.55)个比较,差异均具有统计学意义(t=-2.401、-2.536,P=0.047、0.039);(2)治疗后BDNF组TrkB、BDNF蛋白表达明显增强. 结论 侧脑室内注入BDNF减少了Aβ致密斑的形成,使Aβ蛋白沉积导致的神经毒性作用减弱,从而促进皮层区TrkB表达增强,导致内源性BDNF表达增强,可在一定程度上延缓AD小鼠的病程.     

The C270T polymorphism of the brain-derived neurotrophic factor gene is associated with schizophrenia

We investigated a novel polymorphism of single nucleotide substitution (C270T) of the brain-derived neurotrophic factor (BDNF) gene in schizophrenia patients (n=101) and in controls (n=68). The frequency of the C/T genotype and the T allele were significantly higher in the schizophrenia patients (25.7% and 13.9%, respectively) compared with the controls (5.9% and 2.9%). There were no significant differences in Positive and Negative Symptom Scale (PANSS) items and Global Assessment of Functioning (GAF) scores between the patients with C/C and C/T genotypes. Further studies are warranted to elucidate the significance of this finding in the pathophysiology of schizophrenia.