酪氨酸激酶受体B基因多态性与抑郁症的关联性分析

目的 探讨酪氨酸激酶受体(TrkB)基因多态性与抑郁症的关系.方法 收集抑郁症患者(n=237)和正常对照者(n=312)的外周静脉血,提取基因组DNA.采用TaqMan探针SNP基因分型技术检测两组TrkB基因上的两个单核苷酸多态性的基因分型,并分析基因多态性与抑郁症的关系.结果 抑郁症组与正常对照组TrkB基因rs1187272和rs993315位点基因型和等位基因分布比较,差异均无统计学意义(P>0.05);rs1187272和rs993315位点基因型联合分析显示,两组比较差异也无统计学意义.结论 TrkB基因rs1187272和rs993315及其构成的单体型与抑郁症无显著关联,TrkB基因的多态性在抑郁症的病因学中可能不起主要作用.     

MEK基因多态性与抑郁症的关联性研究

目的研究抑郁症患者丝裂原活化蛋白激酶/细胞外信号调节激酶激酶（MEK）基因的单核苷酸多态性（SNP）,探讨MEK基因与抑郁症发病的关联性。方法采集抑郁症患者（n=425）和健康对照者（n=404）的外周静脉血,提取基因组DNA,采用Taq-Man探针SNP基因分型技术,检测两组受试者MEK1基因（rs1549854和rs4255740位点）和MEK2基因（rs7258366和rs12459484位点）4个SNP位点的基因型,并分析基因多态性与抑郁症的关系。结果①抑郁症组和对照组在rs1549854位点的基因型和等位基因频率比较,差异有统计学意义（P〈0.05）;两组女性受试者比较差异仍有统计学意义（P〈0.01）。②对MEK1和MEK2基因的2个位点分别进行基因型联合分析和疾病风险度分析,发现抑郁症组中rs1549854 AA-rs4255740 CC和rs7258366 AA-rs12459484 GG的联合基因型分布频率均显著高于对照组,且后者危险度最高（OR=2.175,P〈0.01）;而抑郁症组中rs1549854 CC-rs4255740 CT和rs7258366 GG-rs12459484 GG联合基因型分布频率均显著低于对照组,且后者危险度最低（OR=0.132,P〈0.01）。结论①MEK1基因的rs1549854位点可能参与了抑郁症尤其是女性抑郁症的发病。②MEK1/2基因的rs1549854 AA-rs4255740 CC和rs7258366 AA-rs12459484 GG联合基因型可能是抑郁症发病的危险因子,而rs1549854 CC-rs4255740 CT和rs7258366 GG-rs12459484GG联合基因型可能是抑郁症的保护因子。     

MEK基因多态性与抑郁症的关联性研究

目的 研究抑郁症患者丝裂原活化蛋白激酶/细胞外信号调节激酶激酶(MEK)基因的单核苷酸多态性(SNP),探讨MEK基因与抑郁症发病的关联性.方法 采集抑郁症患者(n=425)和健康对照者(n=404)的外周静脉血,提取基因组DNA,采用TaqMan探针SNP基因分型技术,检测两组受试者MEK1基因(rs1549854和rs4255740位点)和MEK2基因(rs7258366和rs12459484位点)4个SNP位点的基因型,并分析基因多态性与抑郁症的关系.结果 ①抑郁症组和对照组在rs1549854位点的基因型和等位基因频率比较,差异有统计学意义(P<0.05);两组女性受试者比较差异仍有统计学意义(P<0.01).②对MEK1和MEK2基因的2个位点分别进行基因型联合分析和疾病风险度分析,发现抑郁症组中rs1549854 AA-rs4255740 CC和rs7258366 AA-rs12459484 GG的联合基因型分布频率均显著高于对照组,且后者危险度最高(OR=2.175,P<0.01);而抑郁症组中rs1549854 CC-rs4255740 CT和rs7258366 GG-rs12459484 GG联合基因型分布频率均显著低于对照组,且后者危险度最低(OR=0.132,P<0.01).结论 ①MEK1基因的rs1549854位点可能参与了抑郁症尤其是女性抑郁症的发病.②MEK1/2基因的rs1549854 AA-rs4255740 CC和rs7258366 AA-rs12459484 GG联合基因型可能是抑郁症发病的危险因子,而rs1549854 CC-rs4255740 CT和rs7258366 GG-rs12459484 GG联合基因型可能是抑郁症的保护因子.     

盘状结构域受体酪氨酸激酶1与炎症关系的研究进展

盘状结构域受体酪氨酸激酶1(DDR1)是新发现的一种受体酪氨酸激酶,可以与其配体——胶原蛋白特异性结合,而这种结合可导致位于胞内区的酪氨酸激酶缓慢而持续的磷酸化,这种磷酸化可参与细胞的增殖、分化、黏附、迁移以及炎症信号通路的活化,进而导致多种病理学的改变,如纤维化和恶性肿瘤的发生、发展。同时,DDR1还可参与多个脏器的炎症反应,如肝炎、肾炎、中枢神经系统炎症等。未来,需进一步研究DDR1是否参与其他脏器的炎症反应,力求全面反映DDR1在炎症中所发挥的作用。     

配体诱导受体酪氨酸激酶活化的结构基础研究进展

受体酪氨酸激酶（RTK）家族是一类具有内源性蛋白酪氨酸激酶（PTK）活性的单次跨膜受体,它们在调控与细胞增殖、分化等相关的信号转导通路中起关键作用。它与配体结合后引起二聚化或结构重排而使胞内区的酪氨酸（Tyr）被自磷酸化。Tyr的自磷酸化一方面可以激活胞内PTK区的活性,另一方面可以为下游的信号蛋白提供结合位点从而完成活化过程。本文对RTK家族成员的晶体结构及其活性调节机制的研究进行了综述,阐述了由配体诱导RTK活化的结构基础,并简要讨论了RTK抑制剂可能的作用靶点。     

膀胱癌受体酪氨酸激酶基因及蛋白的表达

目的 检测膀胱癌受体酪氨酸激酶(RTKs) mRNA和蛋白的表达,探讨有前景的膀胱癌生物标志物及可能的药物靶点.方法 分别采用实时定量PCR芯片技术及蛋白芯片技术,检测浸润性膀胱尿路上皮癌组织中RTKs mRNA及蛋白的表达,以正常膀胱组织作为对照.使用生物信息学方法对检测结果进行比较分析.结果 RTKs家族中的TGFA、STAB1、SERPINE1、ANGPT2、SPINK5、ANGPTL1、PROK1、MDK、CXCL9、GRN、RUNX1、VEGFA、TGFB1在膀胱癌组织中的表达显著上调,EDIL3、FIN、CCL2、PDGFD、FGF13、KITLG、FGF2、SERPINF1、TNF显著下调.ALK、Btk、EphB2、ErbB4、PDGFR-α、ROS、Tie-2、Tyk2、VEGFR3蛋白在膀胱癌组织中高表达,FRK、Fyn、IGF-IR、Insulin R、Itk、JAK1、JAK3、LCK蛋白低表达.结论 靶向血管内皮生长因子/血小板衍生生长因子药物可能在治疗膀胱癌方面发挥积极作用.     

受体酪氨酸激酶EphA1的研究进展

EphA1基因是受体酪氨酸激酶Eph家族中第一个成员,不仅参与胚胎发育和血管生成,而且在正常成人组织中也广泛表达。其独特的受体和配体复合物的结构特点和信号转导模式,使其在肿瘤发生、发展和转移中的作用日益受到重视。在不同器官、不同组织类型的肿瘤,甚至在同一种肿瘤发展的不同阶段,EphA1基因表达状况也有很大差异,提示该基因功能的多元性。深入研究EphA1在血管生成和肿瘤发生、发展和转移中的作用,有可能为肿瘤的早期诊断和治疗提供新的靶点。     

胃癌编码受体酪氨酸激酶的原癌基因研究进展

在多种致癌因子作用下,胃粘膜细胞可发生多个原癌基因的激活及抑癌基因的失活,导致胃癌发生发展,其中编码受体酪氨酸激酶(receptor tyrosine kinase,RTK)的原癌基因,如C-erbB-2及相关的表皮生长因子受体(EGFR)、C-met及K-sam等,在胃癌均以扩增、重排或过度表达等形式高频出现,下面就这些编码RTK原癌基因与胃癌的关系作一综述。     

酪氨酸激酶受体Tie的生物学功能

酪氨酸激酶受体Tie(包含Tie1和Tie2两种类型)是一种能够同配体促血管生成素结合,并将靶蛋白的酪氨酸残基磷酸化的酶联受体之一。Tie主要在血管内皮细胞和造血细胞表面表达,在生长活跃的组织如发育的胚胎、伤口愈合和肿瘤的生长迁移中表达增强。Tie1的配体目前还不清楚,Tie2的配体是血管紧张素。Tie1主要在血管生成、微血管稳定、血管重塑和衰退中发挥调节作用,而Tie2与其配体结合后,可引起血管结构的不稳定。     

肿瘤血管形成与相关的酪氨酸激酶受体

肿瘤的血管在肿瘤浸润、生长、转移中发挥着重要的作用。肿瘤血管的形成及其形成方式一直是人们的研究热点 ,它的阐明将为抗肿瘤血管的治疗提供理论指导。已证实三种受体酪氨酸激酶家族及其配体相互作用在肿瘤血管形成中起着关键的调节作用。1　肿瘤血管形成的方式1.1　血管发生 (vasculogenesis)人胚胎发生的过程中间充质细胞能原位分化为血管内皮细胞 ,形成原始的的血管网络。相类似 ,肿瘤的血管发生是来源于骨髓和外周血的血管内皮前驱细胞 (circulatingendothelialprecursorcells,CEPs)或称为成血管母细胞 ,随血液循环达肿瘤组织微血…     

受体型蛋白酪氨酸磷酸酶R基因多态性与重性抑郁障碍的关联分析

目的探讨受体型蛋白酪氨酸磷酸酶R(PTPRR)基因多态性与重性抑郁障碍(MDD)及其内表型的关联性。方法收集中国北方汉族MDD患者517例(MDD组)和健康志愿者455人(对照组),采用时间飞行质谱技术检测研究对象PTPRR基因的11个单核苷酸多态性(SNPs)位点的多态性,采用UNPHASED软件进行等位基因、基因型、单倍型及数量性状分析。结果单位点分析显示,等位基因频率和基因型分布在MDD组和对照组间差异无统计学意义(校正后P>0.05);单倍型分析显示,三位点单倍型rs1398599(C)-rs2175711(A)-rs4489789(T)(P=0.0023,OR=1.334,95%CI=1.104~1.612)和四位点单倍型rs11178391(C)-rs1398599(C)-rs2175711(A)-rs4489789(T)(P=0.0063,OR=1.281,95%CI=1.059~1.549)均显著增加MDD发病风险;数量性状分析显示,SNP rs2203231的等位基因和基因型分别与韦氏记忆量表(WMS-R)的心智原始分(P=0.0038,P=0.0024)和心智量表分(P=0.0057,P=...     

蛋白激酶B1基因多态性与重性抑郁障碍事件相关电位的关联性研究

目的 探讨重性抑郁障碍患者脑源性神经营养因子(BDNF)磷酸肌醇3-激酶(PI3-K)途径中蛋白激酶B1(PKB1)基因多态性与事件相关电位P300、CNV检测指标的关联性.方法 采用病例对照研究,选取重性抑郁障碍患者91例和与之性别、年龄相匹配的正常对照组65例.2组均于入组当日检测其P300及CNV数据.应用聚合酶链反应(PCR)和DNA直接测序技术,检测样本的PKB1基因多态性.分析重性抑郁障碍及正常对照组间P300、CNV均数差异.比较PKB1 SNP基因型间P300及CNV指标均数的差异.结果 ①与对照组比较,重性抑郁障碍患者的P300为P2潜伏期延长(P＜0.05);P3a、P3b及P3波幅均明显减低(P＜0.01);CNV则为B波幅明显减低(P＜0.01)、RT反应时间明显延长(P＜0.01).②重性抑郁障碍患者P300指标在PKB1基因rs3001371含C等位基因的C/C及C/T合并组与TT组间有统计学差别.C/C及C/T合并组P3a、P3b及P3波幅[分别为(5.93±2.35)μV,(6.51±3.00)μV,(6.27±2.43)μV],低于TT基因型组[(分别为(7.45±2.19)μV,(8.63±3.57)μV,(8.04±2.57)μV],均差异有显著性(P＜0.05).未发现rs3001371基因型间CNV的指标均数差异有显著性(P＞0.05).结论 重性抑郁障碍患者PKB1基因rs3001371多态性与P300主成分波幅相关联,提示遗传因素对重性抑郁障碍记忆及认知功能可能有一定的影响.     

Association between the serotonin 1A receptor C（-1019）G polymorphism and major depressive disorder in the northern Han ethnic group in China

Background Recent studies have suggested that susceptibility to major depressive disorder （MDD） might be related to the serotonin 1A receptor （5-HTR1A） C（-1019）G polymorphism. In this study, we aimed to assess the association between 5-HTR1A C（-1019）G polymorphism and MDD in the Northern Han ethnic group of China.
Methods The C（-1019）G of 5-HTR1A was detected with polymerase chain reaction （PCR） in 400 patients with MDD and 400 unrelated age- and sex-matched healthy control subjects. Association between the C（-1019）G and MDD was statistically analyzed.
Results There was a statistically significant difference between MDD patients and controls in both the genotype distribution （X^2=10.913, df=2, ,P=0.004） and the allele frequency （X^2=10.379, df=1, P=0.001 ）, and a significant difference in the genotype distribution and the allele frequency was found both in the female subjects （Genotype distribution： X^2=15.406, df=2, P=0.000; allele frequency： X^2=15.552, df=1, P=0.000） and the late-onset subjects （Genotype distribution X^2=7.771, df=2, P=0.021 ; allele frequency： X^2=8.007, df=1, P=0.005） in the two groups.
Conclusion These results suggest that 5-HTR1A C（-1019）G polymorphism is probably associated with MDD and it is likely to be the susceptible gene locus for the female and late-onset MDD.     

儿茶酚胺氧位甲基转移酶基因多态性与重性抑郁障碍的关联研究

目的探讨儿茶酚胺氧位甲基转移酶（eateehol一0-methyltransferase,COMT）基因Vall58Met（rs4680）多态性与中国汉族人群重性抑郁障碍（majordepressivedisorder,MDD）之间的关联。方法以250例MDD患者及300例健康对照作为研究对象,应用聚合酶链反应一限制性片段长度多态性（PCR-RFLP）技术测定研究对象的COMTVall58Met的基因型和等位基因频率分布。并采用t检验、Hardy—Weinberg平衡检验及x2检验进行统计学分析。结果病例组与对照组COMTVall58Met基因型及等位基因频率分布均差异有统计学意义（x2=20．268,12．611,P〈0．01）,携带Met等位基因的人群患MDD的危险度是携带Val等位基因的1．725倍（OR=1．725,95％C／1．274～2．335）。结论COMTVall58Met基因多态性与MDD发病有关联,携带Met等位基因的人群患MDD的危险性增加。     

蛋白激酶B1基因多态性与重性抑郁障碍事件相关电位的关联性研究

Objective To explore the relationship of protein kinase B1 ( PKB1 ) gene polymorphisms in PI3-K pathway of BDNF and event-related potentials in depression.Methods The design of case-control research was used ,and 91 major depressive patients and 65 normal controls who were made in age and gender matched with patients were measured auditory event-related potential P300 and contingent negative variation ( CNV ) in the day when two groups were collected.Polymerase chain reaction (PCR) and direct DNA sequencing technology were used to detect PKB1 gene polymorphisms.Three SNPs that named rs3001371 ,rs2494738 ,rs1130214 were selected from 3 representative BLOCK Districts of PKB1.Two independent samples t test was used to analysis P300 and CNV between two groups,and the same way to analysis the average level of P300 and CNV and PKB1 SNP genolatency of P2(P＜0.05) and lower amplitude of P3a(P＜0.01 ) ,P3b(P＜0.01 ) and P3 (P＜0.01 ) ;CNV had der had statistical difference (P＜ 0.05 )in PKB1 rs3001371 gene between C/C and C/T genotype combined which included C allele, and T/T genotype.The amplitude of P3a( (5.93 ± 2.35 ) μV, P3b(6.51 ± 3.00) μV, P3 (6.27±2.43) μV) were lower than TT Genotype ( (7.45 ±2.19)μV, (8.63 ±3.57)μV,(8.04 ±2.57)μV,respectively).The mean of CNV indicators were not found different in statistics among the rs3001371 genotypes.Conclusions PKB1 gene rs3001371 polymorphism is associated with the principal component of P300 amplitude in patients with Major depressive disorder which suggest that genetic factors may have a certain impact on cognitive function in the patients with Major depressive disorder.     

蛋白激酶B1基因多态性与重性抑郁障碍事件相关电位的关联性研究

Objective To explore the relationship of protein kinase B1 ( PKB1 ) gene polymorphisms in PI3-K pathway of BDNF and event-related potentials in depression.Methods The design of case-control research was used ,and 91 major depressive patients and 65 normal controls who were made in age and gender matched with patients were measured auditory event-related potential P300 and contingent negative variation ( CNV ) in the day when two groups were collected.Polymerase chain reaction (PCR) and direct DNA sequencing technology were used to detect PKB1 gene polymorphisms.Three SNPs that named rs3001371 ,rs2494738 ,rs1130214 were selected from 3 representative BLOCK Districts of PKB1.Two independent samples t test was used to analysis P300 and CNV between two groups,and the same way to analysis the average level of P300 and CNV and PKB1 SNP genolatency of P2(P＜0.05) and lower amplitude of P3a(P＜0.01 ) ,P3b(P＜0.01 ) and P3 (P＜0.01 ) ;CNV had der had statistical difference (P＜ 0.05 )in PKB1 rs3001371 gene between C/C and C/T genotype combined which included C allele, and T/T genotype.The amplitude of P3a( (5.93 ± 2.35 ) μV, P3b(6.51 ± 3.00) μV, P3 (6.27±2.43) μV) were lower than TT Genotype ( (7.45 ±2.19)μV, (8.63 ±3.57)μV,(8.04 ±2.57)μV,respectively).The mean of CNV indicators were not found different in statistics among the rs3001371 genotypes.Conclusions PKB1 gene rs3001371 polymorphism is associated with the principal component of P300 amplitude in patients with Major depressive disorder which suggest that genetic factors may have a certain impact on cognitive function in the patients with Major depressive disorder.     

蛋白激酶Cγ亚型基因多态性与重性抑郁障碍的关联性

目的 探讨蛋白激酶Cγ亚型(PKCγ)基因多态性rs3745406与重性抑郁障碍及其症状表型的关联性. 方法 用筛查收集2005年5月至2008年3月在山西医科大学第一医院精神卫生科的门诊或住院部的确诊的中国汉族重性抑郁症患者453例,包括首发蕈性抑郁障碍(80.67％)和部分复发患者(19.33％);采用汉密顿抑郁量表(HAMD)评定病例组症状表型;应用聚合酶链式反应技术(PCR)扩增目的DNA片段,对PCR产物直接测序,检测研究对象rs3745406位点的多态性;使用UNPHASED软件进行等位基因,基因型分析、数量性状分析. 结果 (1)研究样本的基因型分布符合Hardy-Weiberg平衡(X~2=1.46,P=0.25).(2)基因型分布和等位基因频率在重性抑郁障碍患者组和对照组之间差异无统计学意义(P>0.05).(3)PKCγ基因rs3745406位点等位基因与汉密顿抑郁量表(HAMD)自杀临床表型存在明显相关性(X~2=4.746,P=0.0360). 结论 PKCγ基因rs3745406多态性与重性抑郁障碍无明显相关,但与重性抑郁障碍的自杀症状存在显著相关性.     

Association between estrogen receptor β gene Rsa1 polymorphism and depressive disorder in peri-menopausal and menopausal women

Objective: To investigate estrogen receptor β (ERβ) gene Rsa1 polymorphism and concentration of estrogen, FSH and LH in serum in peri-menopausal and menopausal women with depressive disorder. Methods: Seventy-four peri-menopausal and menopausal women with depressive disorder met ICD-10 and CCMD-3 assessment criteria for depressive disorder were recruited. ERβ gene Rsa1 polymorphism was analyzed with PCR-RFLP. Serum levels of estrogen, FSH and LH were measured by magnetism-ELISA. Results: The respective frequency of ERβ gene Rsa1 polymorphism was no significant difference between women with depressive disorder and the healthy women (χ2=1.106,P>0.05). The serum level of estrogen was lower in women with depressive disorder than in the healthy women (P<0.05). No difference was found for FSH and LH between two groups. Conclusion: ERβ gene Rsa1 polymorphism may be not associated with depressive disorder in the peri-menopausal and menopausal women. The serum level of estrogen is associated with depressive disorder in the peri-menopausal and menopausal women.     

Bcl-2基因启动子多态性与重度抑郁症及其临床表型的关联分析

目的探讨中国汉族人群Bel-2基因启动子rs2279115位点多态性与重度抑郁症（MDD）及其临床表型的遗传关联性。方法收集2006年1月-2012年12月在上海交通大学医学院附属精神卫生中心心境障碍科就诊的MDD患者701例（MDD组）和725名健康对照者（正常对照组）作为研究对象,使用17项汉密尔顿抑郁量表（HAMD-17）评定患者的临床表型;采集外周血样本,提取DNA,利用TaqMan荧光探针SNP基因分型技术对rs2279115位点进行分型。结果MDD组与正常对照组间rs2279115位点基因型和等位基因频率分布的差异无统计学意义（P〉0．05）;rs2279115多态性基因型之间HAMD-17总分及抑郁情绪、全身症状因子分的差异有统计学意义（P〈0．05）,携带C／C基因型的MDD患者HAMD-17总分及抑郁情绪、全身症状因子分均显著高于携带C／A或A／A基因型的MDD患者。结论Bel-2基因启动子rs2279115位点可能与MDD临床症状群存在关联。