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.     

肿瘤坏死因子a基因多态性与精神分裂症

近来研究表明异常的免疫功能在精神分裂症的发病中起了重要的作用。提示肿瘤坏死因子a（TNFa）基因可能是精神分裂症的易感基因，本文就TNFa基因多态性与精神分裂症的相关性进行综述。     

肿瘤坏死因子α基因多态性与精神分裂症

近来研究表明异常的免疫功能在精神分裂症的发病中起了重要的作用。提示肿瘤坏死因子α(TNFα)基因可能是精神分裂症的易感基因,本文就TNFα基因多态性与精神分裂症的相关性进行综述。     

肿瘤坏死因子β及其基因多态性与吉兰-巴雷综合征的相关性研究

目的研究肿瘤坏死因子β(TNFβ)水平及其基因多态性与吉兰-巴雷综合征(GBS)的相关性。方法①应用双抗体夹心酶联免疫(ELISA)方法测定48例GBS急性期患者和58名健康人血清TNFβ水平。②采用聚合酶链-限制性片段长度多态性(PCR-RFLP)方法进行TNFβ基因多态性分析。结果①GBS组TNFβ水平为(223.12±36.23)pg/mL较健康对照组(152.24±23.66)pg/mL明显升高,P<0.05。重型组TNFβ水平为(241.98±43.37)pg/mL较轻型组(208.44±20.37)pg/mL明显升高。②GBS组TNFβ1等位基因频率为39.58%,明显高于健康对照组基因频率(25.86%),P<0.05。③基因型为TNFβ1/1和TNFβ1/2的GBS患者TNFβ水平分别为(292.27±25.25)pg/mL和(220.93±14.09)pg/mL,都比基因型为TNFβ2/2的患者TNFβ水平高(195.06±5.56)pg/mL,P<0.05。结论TNFβ1等位基因与GBS的易感性相关。TNFβ基因多态性可能通过调节TNFβ的分泌,从而影响不同个体对GBS的易感性和免疫应答的过程。     

肿瘤坏死因子β基因多态性与吉兰-巴雷综合征不同亚型的关联研究

目的研究肿瘤坏死因子βTNFβ基因多态性与吉兰-巴雷综合征(GBS)的两种主要亚型-急性炎症性脱髓鞘性多发性神经病(AIDP)和急性运动性轴索型神经病(AMAN)的易感性和预后的关系。方法对我院在2008至2011年收治的吉兰-巴雷综合征患者进行电生理标准分型,在疾病高峰期和发病1年后随访时进行Hughes神经功能评分;采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术对41例AIDP患者、52例AMAN患者和98名健康人进行TNFβ基因多态性分析。结果 AIDP组TNFβ基因型分布与对照组没有差别,TNFβG等位基因频率明显高于对照组(37.8%,25%);AMAN组TNFβ基因型分布与对照组相比有差别,TNFβG等位基因频率明显高于对照组(40.4%,25%),P<0.05;GBS重症型患者(Hughes评分4⁶分)TNFβG等位基因频率明显高于对照组(40.6%,25%),P<0.05。GBS预后较差患者(Hughes评分>2分)TNFβG等位基因频率明显高于对照组(47.5%,25%),P<0.05。结论 TNFβG等位基因与GBS两种亚型的易患性有关,携带有TNFβG等位基因患者更倾向有较严重的疾病病程且预后较差。     

肿瘤坏死因子-α基因多态性与复发脑梗死患者阿司匹林不耐受遗传易感性的关系

目的 探讨肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)基因rs1799964,rs1800630位点多态性与复发脑梗死患者阿司匹林不耐受遗传易感性的关系。方法 纳入2020年1月-2020年12月本院收治的80例复发脑梗死患者,其中阿司匹林不耐受组19例,阿司匹林耐受(对照)组61例; 采用美国ABI公司生产的3730XL测序仪对样本TNF-α基因rs1799964,rs1800630位点进行基因测序分型。结果(1)入组人群TNF-α基因rs1799964,rs1800630位点基因型分布符合Hardy-Weinberg 平衡定律(P>0.05);(2)阿司匹林不耐受组rs1799964位点C等位基因频率高于对照组(34.21% V_S 16.39%,P=0.018),rs1800630位点A等位基因频率也高于对照组(28.95% V_S 11.48%,P=0.01),其中rs1800630位点A等位基因(OR=2.579,P=0.046)可能是阿司匹林不耐受的独立危险因素。结论 TNF-α基因rs1799964位点C等位基因及rs1800630位点A等位基因可能是复发脑梗死患者阿司匹林不耐受的易感因素。     

阿尔茨海默病中肿瘤坏死因子-α基因多态性及表达

目的探讨肿瘤坏死因子-α(TNF-α)基因多态性与广东地区汉族人群散发性阿尔茨海默病(SAD)发病易感性的关系。方法采用聚合酶链反应-序列特异性引物(PCR-SSP)方法,检测44例SAD病人(AD组)及45例正常老年人(对照组)TNF-α基因的TNF-α1及TNF-α2等位基因频率。按比值比(OR)作疾病关联分析。用放免法检测两组的血清TNF-α含量。结果AD组的TNF-α2基因频率为0．182,明显高于对照组的0．078(OR=2．635,P=0．039)；AD组血清TNF-α含量为(567．85±102．43) ng/L,明显高于对照组的(389．73±56．68)ng/L(P＜0．05)。结论广东地区汉族人群中,TNF-α基因多态性与SAD有关联．TNF-α2等位基因与SAD的易感性有关。     

胱硫醚-β-合成酶基因多态性与精神分裂症核心家系的关联研究

目的:探讨胱硫醚-β-合成酶(cystathionine-beta-synthase,CBS)基因多态性与精神分裂症的关系。方法:采用聚合酶链式反应和DNA测序技术,检测75个精神分裂症核心家系CBS基因T833C、G919A多态性,采用单倍体相对风险度(haplotyperelativerisk,HRR)分析和传递不平衡检验(transmission disequilibrium test,TDT)分析CBS基因多态性与精神分裂症的关系。结果:所有受检者均未发现CBS基因T833C、G919A多态性,但下游8-9内含子33bp处见G→A突变。患者组G→A突变的基因型频率[GG(82.67%),GA(14.67%),AA(2.66%)]与父母组[GG(81.33%),GA(16%),AA(2.67%)]比较差异无统计学意义(χ2=0.29,P>0.05),患者组G→A突变的等位基因频率[G(90%),A(10%)]与父母组[G(89.33%),A(10.67%)]比较差异也无统计学意义(χ2=0.32,P>0.05)。HRR分析未显示G→A突变与精神分裂症有关联(χ2=0.21,P>0.05),TDT分析未见A等位基因在杂合双亲向患病子女的传递中有优势性(χ2=1.80,P>0.05)。结论:CBS基因多态性可能不是精神分裂症的遗传学危险因素。     

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。     

肿瘤坏死因子α及β基因多态性与多发性硬化关系的研究

目的探讨肿瘤坏死因子α(TNFα)及β(TNFβ)基因多态性与多发性硬化(MS)的相关性。方法采用序列特异性引物和聚合酶链式反应(PCR)、限制性内切酶酶切技术对60例MS患者(MS组)和110例健康者(对照组)的TNFα及β基因多态性进行分析。结果MS组TNFα-308等位基因分布频率与对照组比较有显著性差异(P=0．04),且MS组等位基因A含量(3．3%)与对照组(11．8%)比较也有显著性差异(P=0．008)；MS组TNFβ 252等位基因分布频率与对照组比较有显著性差异(P=0．014),且MS组等位基因A含量(69．2%)与对照组(55．5%)比较也有显著性差异(P=0．014)。结论TNFα-308 A等位基因的多态性与MS的发病有一定负相关,TNFβ 252 A等位基因频率及TNFβ 252 A/A基因分布频率与MS的发病有一定正相关。     

肿瘤坏死因子β基因多态性与多发性硬化的相关性研究

目的 研究肿瘤坏死因子β (tumor necrosis factor β, TNFβ)基因多态性与多发性硬化(multiple sclerosis, MS)的相关性.方法 [1]采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术对58例MS患者和79名健康人进行TNFβ基因多态性分析.[2]对MS组患者分别进行临床EDSS评分等临床资料收集.结果 [1]MS组TNFβ1等位基因频率(45.69%)较健康人(27.85%)明显升高(P＜0.05);[2]基因型为TNFβ1/1、 TNFβ1/2、TNFβ2/2的MS组患者EDSS评分、首次发病年龄、病程及发病次数各组间比较差异均无统计学意义(P＞0.05).结论 TNFβ1等位基因多态性与MS的易患性有关,与EDSS评分、首次发病年龄、病程及发病次数无显著相关性.     

Association between -G308A tumor necrosis factor alpha gene polymorphism and schizophrenia

Dysregulation of the inflammatory response system has been linked to pathophysiology of schizophrenia. Evidence of immune activation has derived from the detection of abnormal levels of proinflammatory cytokines and their receptors in peripheral blood and cerebrospinal fluid from schizophrenic patients. Cytokines are involved in normal CNS development as well as in the pathogenesis of many neuro-psychiatric disorders, acting directly on neural cells or modulating neurotransmitter and neuropeptide systems. In particular tumor necrosis factor alpha (TNFalpha), depending on its concentration, can exert both neurotrophic and neurotoxic effects and influence neural cell growth and proliferation. Moreover, TNFalpha gene is located on the small arm of chromosome 6 (6p21.1-21.3), a locus associated with genetic susceptibility to schizophrenia. We studied the distribution of -G308A TNFalpha gene polymorphism in 84 schizophrenic patients and in 138 healthy volunteers. This biallelic base exchange polymorphism directly affects TNFalpha plasma levels. Frequency of the TNF2(A) allele is significantly increased in schizophrenic patients as compared to controls (P = 0.0042). Genotype distribution is also significantly different (P = 0.0024). TNF2 homozygotes are represented only in the patient group (P = 0.002). These data suggest a potential role of TNFalpha as a candidate gene for susceptibility to schizophrenia and suggest that immune dysregulation in schizophrenic patients could also have a genetic component.     

Association of tumor necrosis factor alpha gene -G308A polymorphism with schizophrenia

BACKGROUND: Tumor necrosis factor alpha (TNFalpha), a cytokine involved in inflammatory processes, has been implicated in the pathophysiology of schizophrenia. The chromosomal location in the major histocompatibility complex (MHC) region on 6p21.1-21.3, a region with evidence for linkage, suggests a role in susceptibility to schizophrenia. Association of the minor (A) allele of the -G308A TNFalpha gene polymorphism with schizophrenia has been reported [Mol. Psychiatry 6 (2001) 79]. METHODS: Association of the -G308A TNFalpha gene and the lymphotoxin alpha (LTalpha)+A252G gene polymorphisms with schizophrenia was studied in 79 sib pair families with linkage in the MHC region and in 128 trio families using the transmission disequilibrium test (TDT). RESULTS: Weak association of the common G allele was detected for TNFalpha -G308A in both samples independently with borderline significance in the sib pair families (0.064) and with a nominally significant value of P=0.022 in the trio families. Combining both samples produced P=0.003, while LTalpha+A252G, located approximately 2-3 kb distally, revealed P=0.03 and the two locus haplotype yielded a P value of 0.001. CONCLUSION: Our data suggests association of the common G allele of the -G308A TNFalpha gene polymorphism with schizophrenia in a sample of 207 families. However, linkage disequilibrium with a different allele of the TNFalpha gene or another gene in the MHC region cannot be excluded.     

肿瘤坏死因子α基因多态性与多发性硬化的相关性研究

目的:研究肿瘤坏死因子α(TNFα)基因多态性与多发性硬化(MS)的相关性。方法:①采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术对58例MS患者和79名健康人进行TNFα基因多态性分析。②对MS组患者分别进行扩展病残状态评分(expanded disability status scale,EDSS)、首次发病年龄、病程、发病次数临床资料收集。结果:①MS组TNFα基因型分布及等位基因频率与正常对照组比较均无明显差异(χ2=0.466,P=0.495;χ2=0.229,P=0.632)。②基因型为TNFα1/1、TNFα1/2、TNFα2/2的EDSS评分、首次发病年龄、病程及发病次数各组间比较差异均无统计学意义(F=0.53,P=0.5914;F=1.34,P=0.2699;F=0.37,P=0.6914;F=0.49,P=0.6182)。结论:TNFα等位基因多态性与MS的易患性、EDSS评分、首次发病年龄、病程及发病次数均无显著相关性。     

No association between the G308A polymorphism of the tumor necrosis factor-alpha gene and schizophrenia

Several linkage analyses in schizophrenia research point to a locus on chromosome 6p22, where the gene coding for tumor necrosis factor-α (TNF-α) is located. A marked influence of antipsychotic medication on TNF-α has been described. As the involvement of an immune process in the pathophysiology of schizophrenia has been discussed, a functional TNF-α polymorphism appears to be a candidate in genetic schizophrenia research. The G308A polymorphism of the TNF-α gene was described to be associated with increased TNF-α production. Boin and colleagues have already described a significant association between the polymorphic allele and schizophrenia, investigating 84 schizophrenic patients (21 % polymorphic allele) and 138 healthy volunteers (11 % polymorphic allele), recruited in Northern Italy. We carried out a replication study including 157 schizophrenic patients and 186 healthy persons, who were recruited in Southern Germany. Psychopathology was additionally monitored by PANSS. We were not able to replicate the findings of Boin et al., as we did not find any difference in allele frequency or genotype distribution between our schizophrenic patients (13.7 % polymorphic allele) and healthy controls (16.9 % polymorphic allele). Moreover, we did not find any association between genotype and psychopathology, as measured by PANSS. The different results between these two studies may be due to ethnic differences. Received: 22 April 2002 / Received in revised form: 3 September 2002 / Accepted: 4 September 2002 Correspondence to Markus J. Schwarz, M. D.     

Association between the tumor necrosis factor-alpha -308 G/A gene polymorphism and migraine

In a group of 299 migraine patients and 306 control subjects, the association of the -308 G/A polymorphism in the tumor necrosis factor-alpha gene (TNFalpha) with the occurrence and clinical characteristics of migraine was tested. Homozygosity for the G allele was associated with an increased risk of migraine (odds ratio [OR] = 2.85, p < 0.001). When the patients were divided into subgroups, the association was confirmed in patients affected by migraine without aura (OR = 3.30, p < 0.001) but not in migraine with aura. These data suggest that the TNFalpha gene or a linked locus significantly modulates the risk for migraine.     

精神分裂症与G72基因多态性的关联

目的：探讨在云南省汉族人群中D-氨基酸氧化酶激活基因（G72）多态性与精神分裂症的关联性。方法：采用聚合酶链式反应-限制性片段长度多态（PCR-RFLP）方法,在云南汉族276例精神分裂症患者和312例健康对照者中进行G72基因3个多态位点（rs9558562,rs45476401,rs3918341）的分型。结果：各位点在病例组和对照组中基因型分布均符合Hardy-Weinberg平衡。无论在男女混合样本,还是分别在男性、女性样本中,rs9558562,rs45476401,rs3918341在病例组和对照组间的等位基因频率分布差异均无显著性（P均〉0.05）。结论：G72基因rs9558562,rs45476401和rs3918341多态与云南汉族精神分裂症发病无显著相关。     

肿瘤坏死因子α基因多态性与吉兰-巴雷综合征的相关性

目的探讨肿瘤坏死因子α(TNFα)水平及其基因多态性与吉兰-巴雷综合征(GBS)的相关性。方法应用双抗体夹心酶联免疫方法测定48例GBS患者和58名健康人血清中TNFα含量。采用聚合酶链-限制性片段长度多态性方法进行TNFα基因多态性分析。结果①GBS组TNFα水平为(47·34±6·12)pg/ml,较健康人[(21·18±5·24)pg/ml]升高(P<0·05)。②GBS组TNF2等位基因频率为20·83%,较健康人(5·17%)明显升高(P<0·05)。③基因型为TNF1/2和TNF2/2的GBS患者TNFα水平分别为(50·76±2·86)pg/ml和(58·07±1·09)pg/ml,较基因型为TNF1/1的患者水平高[(44·46±4·77)pg/ml,P<0·05]。结论TNF2等位基因与GBS的易患性相关。TNFα基因多态性可能通过调节TNFα水平,从而影响不同个体对GBS的易患性和免疫应答的过程。