TNF-α基因多态性与妊娠高血压的相关性研究

目的　探讨肿瘤坏死因子-α(tum or necrosis factor- alpha,TNF-α)基因启动子- 30 8G>A、- 85 0 C>T多态性与妊娠期高血压疾病的相关性。方法　应用聚合酶链反应-限制性片段长度多态性技术检测10 6例患者和10 8名健康孕妇的TNF- α基因启动子- 30 8G>A、- 85 0 C>T多态性。对两组之间的基因型频率和等位基因频率进行比较。结果　TNF-α基因启动子- 30 8位点TNF2等位基因频率和TNF2 / 1基因型频率在病例组明显升高(P<0 .0 5 )。- 85 0位点T等位基因频率和CT+TT基因型频率在对照组明显升高,差异有统计学意义(P<0 .0 5 )。由这两个多态性位点组成的不同基因型中,病例组TNF2 / 1CC基因型频率明显高于对照组,差异有统计学意义(P<0 .0 5 ) ,而TNF1/ 1TT基因型频率在对照组明显增高,差异有统计学意义(P<0 .0 5 )。结论　TNF- α- 30 8、- 85 0位点多态性与妊娠期高血压疾病相关,其中TNF- α基因- 30 8位点的突变是危险因素,- 85 0位点的突变可能是保护性因素。TNF2 / 1CC基因型可能是妊娠期高血压疾病的易感基因型。     

不明原因习惯性流产与肿瘤坏死因子水平及肿瘤坏死因子α-308基因多态性的相关性初步研究

目的研究肿瘤坏死因子(TNF)水平及肿瘤坏死因子α-308 基因多态性与不明原因习惯性流产的关系.方法用放免法测定50例不明原因习惯性流产患者及50例健康对照者血清TNF水平, 用聚合酶链反应扩增TNF-α-308 基因片段,NcoI内切酶进行限制性酶切反应.结果 50例妊娠高血压综合征患者及50例正常对照TNF-α-308基因型及等位基因频率均无显著性差异, 而血浆中TNF水平,不明原因习惯性流产组明显高于对照组(p<0.05).结论炎性反应在不明原因习惯性流产病程中有重要作用,TNFα-308基因多态性与不明原因习惯性流产无关联.     

肿瘤坏死因子α308G/A基因多态性与食管鳞状细胞癌预后的相关性

食管癌是常见的恶性肿瘤之一,影响食管癌预后的因素很多,除肿瘤分级、临床分期、淋巴结转移等,机体的免疫状况和遗传易感性日益受到重视.肿瘤坏死因子(TNF)α是一种具有多种生物活性的致炎细胞因子,由激活的单核巨噬细胞产生.该基因启动子区域转录起始位点上游第308位点存在的G/A等位基因的多态性备受关注.该位点为G时,定义为TNF1,为A时定义为TNF2.     

肿瘤坏死因子基因多态性与疾病

肿瘤坏死因子 (TNF)具有多种生物活性。在许多疾病过程中 ,TNF表达量特征性升高。进一步的研究表明 ,这种升高与TNF基因多态性相关。此种多态性在某种程度上影响TNF的表达。本文就TNF基因多态性影响其转录及与疾病发生发展的相关性作一综述。     

冠心病与肿瘤坏死因子水平及肿瘤坏死因子βG252A基因多态性的相关性初步研究

目的研究肿瘤坏死因子水平及肿瘤坏死因子-βG252A（TNF-β）基因多态性与冠心病的关系。方法用ELISA测定63例冠心病患者及103例健康对照者血清TNF水平,用聚合酶链反应扩增TNF-β第一内含子含有1069位核苷酸A—G多态位点的基因片段。NcoI内切酶进行限制性酶切反应。结果63例冠心病患者和103例正常对照TNF-β基因型及等位基因频率差异均无统计学意义,而血浆中TNF水平,冠心病组明显高于对照组,两组之间比较差异有统计学意义（P〈0．001）。结论血清TNF水平显著升高提示炎性反应在冠心病病程中起重要作用．TNF-β G252A基因多态性与冠心病无关联。     

TNF-α基因多态性在中国人群中的分布及其与冠心病相关性的研究进展

除单核巨噬细胞可以分泌肿瘤坏死因子α（TNF-α）外,心肌细胞也可以合成并分泌TNF—α,当心肌缺血时可诱导心肌细胞表达TNF—α增强。TNF-α可以直接或间接损伤血管内皮细胞,产生促炎症、促凝血、抗纤溶反应,提示其参与冠心病的发生发展过程。TNF-α基因启动子区的多态性位点影响TNF—α基因的表达,TNF—α基因在不同种族和不同地区人群间的多态性分布使冠心病在不同种族、不同地区间具有不同的发病率和临床特点。     

TNF-α基因多态性对雷公藤甲素抑制PBMC分泌TNF-α的影响

目的：TNF—α基因多态性对雷公藤甲素刺激PBMC分泌TNF-α的影响。方法：采用等位基因特异引物PCR法对41名健康志愿者TNF-α基因启动子区-308位点基因多态性进行检测，同时进行外周血单个核细胞（PBMC）培养，用脂多糖（LPS）或雷公藤甲素刺激培养细胞，收集上清液，ELISA法检测上清液中TNF-α的含量。结果：TNF-α -308非G／C纯合子基因型健康志愿者PBMC经LPS刺激后TNF—α的分泌量明显较TNF-α -308G／C纯合子高；雷公藤甲素能够抑制TNF-α -308G／C纯合子基因型健康志愿者PBMC分泌TNF-α，而对TNF-α -308非G／C纯合子基因型健康志愿者PBMC没有明显的抑制作用。结论：肿瘤坏死因子基因多态性与雷公藤甲素刺激外周血单个核细胞分泌TNF—α的量存在一定的联系，推测该基因多态性可能与临床雷公藤治疗类风湿关节炎所产生的个体疗效差异有一定关联。     

SLE患者TNF-β基因多态性分析

系统性红斑狼疮（SEE）是一种累及多系统、具有多种自身抗体的自身免疫性疾病,遗传因素在SLE发病机制中起重要作用。肿瘤坏死因子（TNn是具有多种生物学功能的细胞因子,体内外实验证实,TNF水平与SLE的活性指标密切相关。鉴于TNF基因的特殊位置及TNF的重要生物学活性,TNF的基因多态性与SLE的发病、病程及预后之间的关系已引起普遍关注。我们早期研究发现．TNF—α基因多态性与SLE发病相关,为探讨TNF-β基因的多态性与SLE的关系．     

TNF-α和TNF受体在大鼠坐骨神经炎症中的表达变化

肿瘤坏死因子(turnour necrosis fac-tor,TNF)能够引起炎症,具有抗病毒和免疫调节作用,可引起肿瘤细胞溶胞及抑制其生长.本实验主要研究TNF-α及TNF受体在LPS诱导大鼠坐骨神经炎症中的表达变化及分布情况,以探索其在周围神经损伤后炎症过程中,可能发挥的作用和意义.     

阿茨海默氏病与肿瘤坏死因子水平及肿瘤坏死因子TNF-α-308G／A基因多态性的关系

目的探讨肿瘤坏死因子A-308基因多态性与阿茨海默氏病的关系。方法用放免法测定TNF水平，运用多聚酶链反应技术检测66例阿茨海默氏病及143例正常人肿瘤坏死因子A-308基因多态性。结果AD组肿瘤坏死因子A-308TNF-α1／1、TNF-α1／2、TNF-α2／2表型频率分别为0．8636、0．1212、0．0152。对照组分别为0．8881、0．1049、0．070；AD组TNF-α1、TNF-α2基因频率分别为0．9242、0．0758；对照组分别为0．9021、0．0979。肿瘤坏死因子A-308各种基因型频率在患者组与正常对照组之间的差异无显著性（P〉0.05），而血浆中TNF水平。阿茨海默氏病组明显高于对照组，两组之间比较差异有统计学意义（P〈0．05）。结论血清TNF水平显著升高．提示炎性反应在Alzheimer病程中有重要作用，肿瘤坏死因子A-308基因多态性与AD无明显相关。     

TNF alpha promoter polymorphisms analysis in benign and malignant breast lesions

Polymorphisms in genes involved in the complex mechanisms of carcinogenesis may affect the susceptibility to cancer. The multifunctional cytokine tumor necrosis factor alpha (TNF alpha) has an important role in the pathogenesis of inflammatory, autoimmune and malignant diseases. It has a large spectrum of activities, including both antitumorigenic and protumorigenic. In recent years, several TNF alpha promoter polymorphisms have been identified and related to the expression level of cytokine and to the susceptibility to solid tumors. The aim of our study was to investigate the frequency of three TNF alpha promoter polymorphisms (-1031, -308 and -238) in benign (fibrocystic changes) and malignant (invasive carcinoma) breast lesions. Using "real-time" PCR SNP analysis these polymorphisms were determined in 76 patients with benign and 158 patients with malignant breast lesions. The high expression genotypes at any of the three SNP polymorphisms were more frequent in invasive breast carcinoma (in 81 of 158 examined, 51.3%) than in fibrocystic changes (in 33 of 76 examined, 43.4%). The combined frequency of high production genotypes (-1031 T/C and C/C, -308 G/A and A/A and -238 G/A and A/A) was higher in patients with invasive breast carcinoma than in those with fibrocystic changes. However, these results were not statistically significant. Further studies on a larger group of patients are needed to evaluate the significance of potential differences in TNF alpha genotypes in different breast lesions.     

Complex haplotypic structure of the central MHC region flanking TNF in a West African population

TNF polymorphisms have been associated with susceptibility to malaria and other infectious and inflammatory conditions. We investigated a sample of 150 West African chromosomes to determine linkage disequilibrium (LD) between 25 SNP markers located in an 80 kb segment of the MHC Class III region encompassing TNF and eight neighbouring genes. We observed 45 haplotypes, and 22 of them comprise 80% of the sample. The pattern of LD is remarkably patchy, such that many markers show no LD with adjacent markers but high LD with markers that are much further away. We introduce a method of examining the implications of LD data for disease association studies based on sample size considerations: this shows that certain TNF polymorphisms would be likely to yield positive associations if the true disease allele resided in LTA or BAT1. We conclude that detailed marker maps are needed to resolve the causal origin of disease associations observed at the TNF locus.     

Alleles 308A and 238A in the tumor necrosis factor alpha gene promoter do not increase the risk of severe malaria in children with Plasmodium falciparum infection in Mali

The hypothesis that tumor necrosis factor (TNF) aggravates malaria in children is supported by observations that TNF polymorphisms and high TNF levels have been associated with cerebral malaria. Nevertheless, severe malaria was not associated with polymorphisms located at positions -308A and -238A in the TNF alpha gene promoter or with a high TNF level in plasma in children from Bamako, Mali.     

Interethnic studies of TNF polymorphisms confirm the likely presence of a second MHC susceptibility locus in ankylosing spondylitis

The objective of this study was to investigate TNF promoter region polymorphisms for association with susceptibility to ankylosing spondylitis (AS). The TNF -238 and -308 polymorphisms were genotyped in 306 English AS cases and 204 ethnically matched healthy B27-positive controls, and 96 southern German AS cases, 58 B27-positive and 251 B27-negative ethnically matched controls. Additionally, the TNF -376 polymorphism was genotyped in the southern German cases and controls. In the southern German AS patients a significant reduction in TNF -308.2 alleles was seen, compared with B27 positive controls (odds ratio 0.4, P = 0.03, 95% confidence interval 0.2-0.9), but no difference in allele frequencies was observed at TNF -238. Significant association between AS and both TNF -238 and TNF -308 was excluded in the English cases. These results confirm previous observations in the southern German population of association between TNF promoter region polymorphisms and AS, but the lack of association in the English population suggests that these polymorphisms themselves are unlikely to be directly involved. More likely, a second, non-HLA-B, MHC locus is involved in susceptibility to AS in these two populations.     

TNF as a malaria candidate gene: polymorphism-screening and family-based association analysis of mild malaria attack and parasitemia in Burkina Faso

We have previously obtained strong evidence for linkage of mild malaria attack to the MHC region, with a peak close to the tumor necrosis factor (TNF) gene. We screened, for polymorphisms, the entire TNF gene in the same sample of 34 families comprising 197 individuals living in a Plasmodium falciparum endemic area and we found 17 polymorphisms. In a longitudinal study, we investigated whether the 11 most frequent and informative polymorphisms were associated with mild malaria attack and maximum parasitemia, which was the highest parasitemia in each individual over 2 years. Mild malaria attack and maximum parasitemia were positively correlated. Transmission disequilibrium tests showed nominal evidence for association between TNF-1031, TNF-308, TNF851 and TNF1304 polymorphisms, and mild malaria attack on the one hand, and between TNF-238, TNF851 and TNF1304 polymorphisms, and maximum parasitemia on the other hand. After accounting for multiple tests, we confirmed the association of TNF-238 with maximum parasitemia and the association of TNF1304 and TNF851 with maximum parasitemia and mild malaria attack. The association tests with mild malaria attack suggest a moderate effect of TNF-308 polymorphism. In conclusion, our study suggests that several TNF variants may be part of the genetic determinants for maximum parasitemia and/or mild malaria attack.     

The alteration of mitochondria is an early event of arsenic trioxide induced apoptosis in esophageal carcinoma cells

It is accepted that inorganic arsenic trioxide is an inducer of apoptosis for many types of cancer. Our previous studies have demonstrated that arsenic trioxide induces apoptosis of esophageal carcinoma cells. Administration of arsenic trioxide results in the inhibition of growth and survival of tumor cells. Esophageal carcinoma cells treated with arsenic trioxide for 3 days demonstrated a typical morphological appearance of apoptosis. To further examine molecular mechanism of arsenic trioxide induced apoptosis of esophageal carcinoma cells, we have investigated the early changes of the apoptotic cell induced by arsenic trioxide. Our results indicated that arsenic trioxide induced apoptosis of esophageal carcinoma cells occurs as early as 2 h after treatment. Annexin-v staining has further proved that the phosphatidylserine is exposed at 2 h. The early morphological change of arsenic trioxide treated cells was in the mitochondria. Arsenic trioxide treated cells displayed aggregated mitochondria. It induces accumulation of high electron-density amorphous substances, swollen and disruption of mitochondria in oesophageal carcinoma cells after 2 h treatment. The alteration of mitochondria induced by arsenic trioxide seems to occur before the condensation of chromatin. Thus, our data demonstrated that the primary target of arsenic trioxide induced apoptosis of esophageal carcinoma cells may be the mitochondria. It is possible that arsenic trioxide is a mitochondriotoxic agent.     

抑癌基因PTEN与食管癌

PTEN是近年发现的一种与细胞信号传导途径有关的具有双特异性磷酸酶活性的新型抑癌基因。研究表明,该基因的突变与人类多种恶性肿瘤的发生发展密切相关。近年来国内外的学者在食管癌组织中发现,虽然该基因发生突变的频率较低,但其蛋白表达却普遍下降,表达程度与食管癌的恶性程度及预后密切相关。因此,PTEN的低表达可能参与了食管癌的发生发展过程。     

High expression of TNF alpha is associated with −308 and −238 TNF alpha polymorphisms in knee osteoarthritis

Knee osteoarthritis (OA) is a common chronic degenerative disease characterized by the loss of articular cartilage components due to an imbalance between extracellular matrix destruction and repair. The proinflammatory cytokines involved in OA, TNFα and IL1β, are considered the major implicated. The aim of this study was to investigate the relationship between TNFα ?308 and ?238 polymorphisms with messenger RNA (mRNA) and soluble TNFα expression in knee OA patients and healthy subjects (HS). Case–control study involved 50 knee OA patients classified according to 1986 ACR Classification Criteria, as well as 100 HS. The Western Ontario and McMaster Universities Osteoarthritis Index and Lequesne disability index were applied to OA patients. The ?308 and ?238 polymorphisms were determined by polymerase chain reaction–restriction fragment length polymorphism technique. The TNFα mRNA expression was quantified by real-time PCR using TaqMan method. The sTNFα levels were measured by enzyme-linked immunosorbent assay. The TNFα mRNA expression in knee OA patients was higher than in HS (1.56-fold). In addition, the TNFα mRNA expression was higher in carriers of G allele in the knee OA group for both polymorphisms. The sTNFα levels were increased in G/G versus G/A genotypes in both studied polymorphisms (p < 0.05). However, the TNFα ?308 and ?238 genotypes did not show statistical differences between groups. The G allele of TNFα ?308 and ?238 polymorphisms is associated with high mRNA and soluble expression in knee OA patients. However, it is not a marker of susceptibility in Western Mexico. Further studies are necessary to confirm these findings.     

食管癌患者治疗前后血清TNF,SA和SIL-2R检测的临床意义

目的 :探讨食管癌患者治疗前后血清中肿瘤坏死因子 (TNF)、唾液酸 (SA)和白细胞介素 - 2受体(SIL - 2R)含量。方法 :应用放射免疫分析和分光光度计法对 38例食管癌患者进行了治疗前后血清TNF、SA、SIL - 2R含量检测。并以 35名正常健康人作比较。结果 :治疗前食管癌患者血清TNF、SA、SIL - 2R水平均非常显著地高于正常人组 (P <0 .0 1) ,治疗后 2个月则与正常人组比较无显著性差异 (P >0 .0 5 )。结论 :食管癌患者血清中TNF、SA、SIL - 2R含量与该病的发生和发展密切相关。     

Polymorphisms in or near tumour necrosis factor (TNF)-gene do not determine levels of endotoxin-induced TNF production

Innate differences in tumour necrosis factor (TNF) production have been associated with susceptibility for and outcome of inflammatory diseases. Several studies have tried to identify whether polymorphisms in or near the TNF gene or other markers on the short arm of chromosome 6 (6p21) are related to differences in TNF production. Data on these associations are conflicting. Therefore, we conducted a study among 129 healthy individuals in which TNF production was determined upon stimulation with endotoxin in whole blood cultures. TNFa microsatellite, TNF single nucleotide polymorphisms at position +489, -238, -308 and -376 typing was performed. The data revealed that alleles of TNFa microsatellite and carriership of TNF polymorphisms were not related to TNF production. We conclude that the genes determing the differences in endotoxin-induced TNF production have not been yet identified.