脑胶质瘤易感基因PLA2G4C的短串联重复序列多态性的初步研究

目的运用分子生物学方法筛查脑胶质瘤易感基因PLA2G4C的短串联重复序列的多态性，并进一步确定这些多态性与脑胶质瘤发病的关系。方法以天坛医院为主收集入院脑胶质瘤病人和对照组的血液及肿瘤组织，对肿瘤和血液标本分别进行DNA提取，对基因PLA2G4C的特定片段进行PCR扩增，利用变性高效液相色谱及琼脂糖凝胶电泳等技术进行比较研究，推测突变的意义。结果本组共收集标本223份，通过琼脂糖凝胶电泳检测到了短串联重复序列，通过变性高效液相色谱技术检测到了纯合峰及杂合峰。结论PLA2G4C的短串联重复序列多态性与胶质瘤的发病有一定关系，并可通过血液标本进行此多态性的筛查。DHPLC是一种高效、经济、简便可靠的基因多态性的筛选方法。     

细胞色素P4502D6C188T基因多态性与难治性抑郁症的关联

目的:探讨细胞色素P450(CYP)2D6 C188T基因多态性与难治性抑郁症及氟西汀合并小剂量利培酮治疗的疗效、不良反应的关联.方法:应用聚合酶链反应(PCR)扩增技术及限制性片段长度多态性(RFLP)测定92例难治性抑郁症患者及107名正常对照的CYP2D6 C188T基因多态性.其中59例患者接受氟西汀合并小剂量...     

载脂蛋白E基因多态性与缺血性脑血管病的关系

目的载脂蛋白E(apoE)基因多态性对缺血性脑血管疾病(ICVD)发生的影响。方法临床筛选67例缺血性脑血管病病人,利用聚合酶链反应(PCR)技术进行apoE基因位点的扩增,然后用HhaⅠ酶切DNA扩增产物,进行限制性片断长度多态性分析(RFLP),检测他们的apoE基因型,并与正常对照组比较,并同时检测血脂水平及血流变学指标。结果ICVD组与健康对照组apoE基因型分布无显著差异,不同类型ICVD组apoE基因型分布亦无显著差异。结论apoE基因多态性不是缺血性脑血管病的危险因素。     

载脂蛋白B基因多态性与动脉粥样硬化性疾病

载脂蛋白B(ApoB)基因多态性与动脉粥样硬化性疾病如冠心病、脑卒中等的关系成为近年来的研究热点。ApoB基因多态性主要表现为:限制性片段长度(RFLP)多态性,其中X+等位基因、E-等位基因和M-等位基因的分布频率在中国人中分布较低;信号肽编码区插入/缺失(Ins/Del)多态性;3’端可变数目串联重复序列(VNTR)多态性。这些基因的多态性与血脂异常、动脉粥样硬化及心脑血管疾病存在一定的关系。     

脑梗死患者血清对氧磷酶基因192位点多态性检测

目的　建立检测脑卒中患者血清对氧磷酶 (Paraoxonase ,PON)基因 192位Arg/Glu多态性的简便实用方法。方法　碘化钠 (NaI)法提取外周血白细胞DNA ,应用多聚酶链反应 (PCR)对PON1基因酶切位点的限制性片段长度多态性 (RFLP)进行分析。结果　扩增产物经限制性内切酶消化后分别得到三种类型产物即 99bp一条带 ;33bp、6 6bp两条带 ;33bp、6 6bp、99bp三条带。所代表的PON1基因型分别为QQ型、RR型和QR型。结论　该检测方法对脑梗死患者具有简便、实用、特异性高、灵敏度好等优点 ,适于临床科研推广应用     

胞浆型磷脂酶A2基因多态性与精神分裂症的关系

目的：分析印度人群钙依赖性胞浆型磷脂酶A2（cPLA2)BanⅠ限制性内切酶基因多态性与精神分裂症的相互关系。方法：应用聚合酶链式反应（PCR）限制性片段长度多态性（RFLP）方法,在89例精神分裂症患者和78例健康人群中观察比较cPLA2等位基因和基因型频数分布。结果：PCR产物的BanⅠ限制性酶切片段于cPLA2基因第一非编码区显示多态性位点,命名为位点A;患者组和健康对照组cPLA2等位基因频数呈显著差异（P＜0．02）;精神分裂症患者显示A2／A2纯合基因型显著增加（P＜0．02）。结论：cPLA2基因多态性与印度人群精神分裂症相关联;cPLA2基因可能为精神分裂症候选基因之一,或与其他致病基因呈连锁不平衡。     

新疆维吾尔族帕金森病患者Parkin基因V/L380多态性研究

目的 研究新疆维吾尔族帕金森病(PD)患者Parkin基因V/L380位点的多态性.方法 提取56例维吾尔族原发性PD患者(PD组)和82例维吾尔族健康对照者(正常对照组)的基因组DNA,采用PCR扩增所需Parkin基因第10外显子基因片段,用限制性内切酶酶切技术检测其Parkin基因V/L380位点的基因型和等位基...     

北方汉族人PLA2R1基因多态性与脑梗死关系的研究

目的探讨中国北方汉族人群PLA2R1基因多态性与脑梗死的关系。方法选取年龄、性别匹配的中国北方汉族脑梗死患者212人,健康对照组179人,采用PCR技术和限制性内切酶片段长度多态性(RFLP)的方法检测基因型。结果PLA2R1基因SNP的等位基因和基因型在脑梗死组和对照组的频数分布差异无显著性(P>0.05)。结论中国北方汉族人群中PLA2R1基因多态性与脑梗死的发病可能无关。     

帕金森病患者PINK1 LRRK2基因单核苷酸多态性分析

目的探讨PINK1基因rs45530340位点及LRRK2基因rs1491942位点单核苷酸多态性(single nucleotide polymorphism,SNP)与淮海地区汉族人群晚发散发性帕金森病(Parkinson’s disease,PD)的相关性。方法收集152例晚发散发性PD患者和160例年龄和性别相匹配的健康对照者,入组者均来自淮海地区汉族人群。提取外周血全基因组DNA,应用聚合酶链式反应(polymerase chain reaction,PCR)技术扩增包含多态位点的目的基因片段,通过琼脂糖凝胶电泳(AGE)检测PCR产物。对PCR产物分别用DNA限制性内切酶NlalV和SmlI进行酶切,用聚丙烯酰胺凝胶电泳(PAGE)、硝酸银染色检测酶切产物,采用聚合酶链式反应-限制性片段长度多态性(restriction fragment length polymorphism,RFLP)技术分析基因型,计算所有研究对象两个SNP位点的基因型频率和等位基因频率。结果 (1)PINK1基因rs45530340位点基因型和等位基因在晚发散发性PD组和正常对照组中的分布无统计学差异(基因型:χ2=1.572,P=0.456;等位基因:χ2=1.318,P=0.251)。(2)LRRK2基因rs1491942位点基因型和等位基因在晚发散发性PD组与正常对照组中的分布差异有统计学意义(基因型:χ2=6.802,P=0.033;等位基因C:χ2=7.448,P=0.006,OR=1.571,95%CI=1.135~2.176)。结论 (1)PINK1基因rs45530340多态位点可能不是淮海地区汉族人群晚发散发性PD患者的危险因素。(2)LRRK2基因rs1491942多态位点C等位基因可能是淮海地区汉族人群晚发散发性PD患者的危险因素。     

脑胶质瘤易感性与ERCC2基因第751号密码子多态性的关系

目的 探讨ERCC2基因第751密码子多态性和胶质瘤易感性的关系.方法 提取ERCC2基因751密码子多态性与脑胶质瘤易感性的关系的数据,筛选出符合条件的数据,应用Meta分析技术的各个软件对各项数据进行异质性检验,计算合并OR值及95％可信区间,并行发表偏倚的评估.结果 本研究中共有5组符合条件的数据,病例组2 307例、对照组3 455例.Meta分析合并结果显示13181A等位基因能够降低高加索人脑胶质瘤的发病风险(P =0.02,OR =0.91; 95％ CI0.84 ～0.98,Pheterogeneity=0.28).结论 ERCC2基因第751号密码子的多态性能够降低高加索人的脑胶质瘤的发病风险.     

胶质瘤术后组织中LGR5D和ERCC1的表达及对预后的判断价值

目的分析LGR5D和ERCC1在胶质瘤患者术后阳性表达情况,并评价LGR5D和ERCC1阳性表达与患者生存质量的关系。方法观察组选择82例胶质瘤术后患者,对照组选择82例急性颅脑损伤并行内减压术切除脑组织（脑组织正常）患者。使用免疫组织化学方法检测LGR5D和ERCC1阳性表达率,并统计不同肿瘤直径、Ki6、肿瘤分期患者的LGR5D和ERCC1表达阳性率,探讨LGR5D和ERCC1与术后生存质量的关系。结果观察组中LGR5D和ERCC1阳性率显著高于对照组（P〈0.05）。观察组肿瘤直径〉2cm、Ki67〉25%、肿瘤分期Ⅲ-Ⅳ期患者的LGR5D和ERCC1阳性率显著高于肿瘤直径≤2cm、Ki67≤25%、肿瘤分期Ⅰ-Ⅱ期患者（P〈0.05）。胶质瘤患者的LGR5D和ERCC1表达具有协同作用,并与患者生存质量有明显的负相关关系。结论 LGR5D和ERCC1在胶质瘤患者中的阳性率较高,而且存在协同效应。通过分析LGR5D和ERCC1的表达,可以有效判断患者病情,判断预后,提升治疗效果。     

胶质瘤化疗药物相关标志分子在胶质瘤与正常脑组织中的丰度比较

目的检测并比较常用胶质瘤化疗药物相关标志分子在胶质瘤组织与正常脑组织中的丰度。方法检测并比较MGMT、ERCCl、TopoⅡα和Stathmin在46例不同病理级别胶质瘤标本及6例正常脑组织中的丰度,比较同一病理级别胶质瘤中这些标志分子的变异度。结果正常脑组织中MGMT和ERCCl的丰度显著高于各级别胶质瘤组织（P〈0．05）,而TopoⅡα的丰度则显著低于各级别胶质瘤组织（P〈0．05）,Stathmin的丰度在正常脑组织与各级别胶质瘤中均无显著性差异。这4种标志分子的丰度在不同级别胶质瘤之间差异均无统计学意义,而在同一级别胶质瘤中的变异度均较大。结论在胶质瘤组织中,MGMT、ERCCl、TopoⅡα和Stathmin的丰度在不同个体间波动很大,实行胶质瘤的个体化丰度检测和个体化化疗会更有益。     

PADI4 gene in multiple sclerosis: a family-based association study

In multiple sclerosis (MS) MBP is heavily citrullinated by peptidylarginine deiminase (PAD). This post-translational modification may be crucial for its pathogenesis. PADI4 is the isoform expressed in inflammatory infiltrates. The aim of this study was to analyse the role of PADI4 gene in conferring susceptibility to MS, by means of a family-based association study, testing three SNPs by RFLP. No association was found either with single SNPs or haplotypes. Similarly no significant association was detected partitioning the patients according to DRB1*15 positivity or disease severity. These results do not support a major role of the PADI4 gene, but further studies may contribute to clarify the genetic factors that regulate deimination.     

Association Between Genetic Variations of Vascular Endothelial Growth Factor Receptor 2 and Glioma in the Chinese Han Population

Tumor angiogenesis, which is an important step in the development of cancer, is directly regulated by vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we examined the association of five potentially functional VEGFR-2 polymorphisms with glioma risk in a Chinese Han population. Three SNPs, rs2071559, rs7667298 and rs2305948, showed a statistically significant increased association with the risk of glioma (P?=?0.006, 0.005, and 0.012, respectively). Both haplotype and diplotype analyses consistently revealed that subjects carrying two copies of the haplotype "CGT" had a 42% reduced glioma risk compared with their respective noncarriers. Our findings suggested that VEGFR-2 gene variants might contribute to glioma susceptibility.     

Association study of the human FZD3 locus with schizophrenia.

The FZD3 protein is a transmembrane receptor for secreted Wnt glycoproteins involved in the Wnt signal transduction cascades. The alteration of Wnt signal transduction cascades has been thought to be involved in producing the cytoarchitectural defects observed in schizophrenia. Because the human FZD3 gene is mapped to chromosome 8p21, which is a potential region containing a gene for schizophrenia, it may play a role in conferring susceptibility to the disease.This study was conducted with the detection of three single nucleotide polymorphisms (SNPs) located within the FZD3 locus by using the polymerase chain reaction-based restriction fragment length polymorphism (RFLP) analysis among 246 schizophrenic family trios of Chinese Han descent.The transmission disequilibrium test (TDT) demonstrated that the three SNPs all showed a preferential transmission with a p value ranging from.0003-.000007. The global chi-squared test for haplotype transmission also showed a strong association (chi(2) = 48.84, df = 7, p <.000001).The strong association between the FZD3 locus and schizophrenia suggests that the gene itself may play a role in underlying schizophrenia, although a nearby gene responsible for predisposing to the illness cannot be ruled out.     

lncRNA MIR4435-2HG的表达水平及甲基化状态与脑胶质瘤病理分级的关系

目的 探讨长链非编码RNA MIR4435-2HG的表达水平及甲基化状态与脑胶质瘤病理分级的关系.方法 选取2019年1～12月手术切除的脑胶质瘤组织110例和颅脑损伤内减压术中切除正常脑组织20例(对照组).采用实时荧光定量PCR和甲基化特异性PCR检测组织和血清MIR4435-2HG水平及甲基化状态.结果 110例...     

IDH突变调控BMP2、COL27A1和SERPINA5基因表达影响人脑胶质瘤的生存预后

目的 探讨异柠檬酸脱氢酶（IDH）突变影响胶质瘤临床预后的潜在分子机制。方法 计算机检索CGGA和TCGA数据库,获取胶质瘤RNA测序数据（RNA-seq）,应用生物信息学分析方法分析IDH突变改善胶质瘤临床预后的潜在分子机制。结果从TCGA数据库下载胶质母细胞瘤（GBM）和低级别胶质瘤（LGG）相关RNA-seq,从CGCA数据量下载648例胶质瘤的RNAseq(234例GBM和414例LGG),从GEO数据量下载单细胞RNA-seq数据GSE131928数据集（28例IDH野生型GBM）。GO和KEGG分析显示,IDH突变显著下调胞外基质（ECM）相关基因表达,GEPIA分析显示BMP2、COL27A1、SERPINA5、VEGFA基因表达水平与胶质瘤生存预后有关,多因素Cox比例回归风险模型分析显示BMP2、COL27A1、SERPINA5基因表达是胶质瘤生存预后独立影响因素,BMP2联合SERPINA5预测胶质瘤生存预后效果最好。结论 我们结果提示胶质瘤IDH基因突变,可能通过调控BMP2、COL27A1和SERPINA5基因表达,影响病人生存预后。     

人脑胶质瘤组织BIRC2表达变化及临床意义

目的 探讨人脑胶质瘤组织含杆状病毒IAP重复蛋白2（BIRC2）表达变化及临床意义。方法 从GEO数据库获取人脑胶质瘤的基因表达芯片进行差异表达基因分析,并借助TCGA数据库对筛选出的BIRC2基因在人脑胶质瘤中的表达及预后进行分析,同时通过GSEA分析BIRC2在人脑胶质瘤中的作用机制进行预测。结果 从GEO数据库筛选GSE66354芯片中筛选出BIRC2为上调表达基因。TCGA数据库分析结果表明,BIRC2在多形性胶质母细胞瘤中的表达显著高于正常脑组织（P<0.05）,预后分析表明BIRC2高表达胶质瘤病人预后更差（P<0.05）,GSEA分析显示BIRC2的作用主要发生在蛋白质翻译启动等过程。结论 本文结果提示BIRC2可能与人脑胶质瘤的发生、发展有关,检测BIRC2基因可用于评估人脑胶质瘤病人预后。     

Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities

PURPOSE: SCN1A is the most clinically relevant epilepsy gene, most mutations lead to severe myoclonic epilepsy of infancy (SMEI) and generalized epilepsy with febrile seizures plus (GEFS+). We studied 132 patients with epilepsy syndromes with seizures precipitated by fever, and performed phenotype-genotype correlations with SCN1A alterations. METHODS: We included patients with SMEI including borderline SMEI (SMEB), GEFS+, febrile seizures (FS), or other seizure types precipitated by fever. We performed a clinical and genetic study focusing on SCN1A, using dHPLC, gene sequencing, and MLPA to detect genomic deletions/duplications on SMEI/SMEB patients. RESULTS: We classified patients as: SMEI/SMEB = 55; GEFS+= 26; and other phenotypes = 51. SCN1A analysis by dHPLC/sequencing revealed 40 mutations in 37 SMEI/SMEB (67%) and 3 GEFS+ (11.5%) probands. MLPA showed genomic deletions in 2 of 18 SMEI/SMEB. Most mutations were de novo (82%). SMEB patients carrying mutations (8) were more likely to have missense mutations (62.5%), conversely SMEI patients (31) had more truncating, splice site or genomic alterations (64.5%). SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS compared to those with missense mutations and without mutations (p = 0.00007, ANOVA test). None of the remaining patients with seizures precipitated by fever carried SCN1A mutations. CONCLUSION: We obtained a frequency of 71%SCN1A abnormalities in SMEI/SMEB and of 11.5% in GEFS+ probands. MLPA complements DNA sequencing of SCN1A increasing the mutation detection rate. SMEI/SMEB with truncating, splice site or genomic alterations had a significantly earlier age of onset of FS. This study confirms the high sensitivity of SCN1A for SMEI/SMEB phenotypes.