Association of bladder tumors and GA genotype of-308 nucleotide in tumor necrosis factor-alpha promoter with greater tumor necrosis factor-alpha expression
Association of bladder tumors and GA genotype of-308 nucleotide in tumor necrosis factor-alpha promoter with greater tumor necrosis factor-alpha expression
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DOI：
10.1016/j.urology.2004.06.018
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发表时间：
2004-11-01
期刊：
影响因子：
2.1
通讯作者：
Kim, WJ
中科院分区：
文献类型：
--
作者：
Jeong, P;Kim, EJ;Kim, WJ
目标.目的探讨肿瘤坏死因子-α（TNF-α）基因启动子区-308位核苷酸多态性与膀胱癌的关系。通过基于聚合酶链反应的限制性片段长度多态性分析来自血液和肿瘤的DNA样本，以表征TNF-α启动子中-308核苷酸的遗传多态性。采用竞争性定量聚合酶链反应检测TNF-α mRNA表达水平，采用酶联免疫吸附法检测血清TNF-α浓度。膀胱肿瘤患者和对照组的-308核苷酸的遗传多态性没有差异（P = 0.259）。然而，肿瘤分级与GA表型的关系具有统计学意义（P = 0.04）。GA基因型的TNF-α mRNA浓度也显著高于GG基因型（P = 0.022）。对于患者和对照组，GA基因型的TNF-α血清水平显著高于GG基因型。然而，膀胱肿瘤患者血清中GG和GA基因型的TNF-α水平显著高于对照组（GG型，P = 0.001; GA型，P = 0.009）。TNF-α启动子中-308核苷酸的基因型对TNF-α的产生具有统计学显著性影响，并且与膀胱肿瘤分级相关。GA多态性可能与基因转录的统计学显着增加。膀胱肿瘤患者的TNF-α血清水平高于对照组，这表明高TNF-α产生与膀胱肿瘤的发展有关，膀胱肿瘤可能分泌TNF-α。(C)2004年爱思唯尔公司
Objectives. To investigate whether the genetic polymorphism of the -308 nucleotide in the tumor necrosis factor-alpha (TNF-alpha) promoter is associated with bladder cancer.Methods. DNA samples from blood and tumor were analyzed by polymerase chain reaction-based restriction fragment length polymorphism to characterize the genetic polymorphism of the -308 nucleotide in the TNF-alpha promoter. TNF-alpha mRNA expression levels were assessed by quantitative competitive polymerase chain reaction, and the serum concentrations of TNF-alpha were measured using enzyme-linked immunosorbent assay.Results. Patients with bladder tumor and control subjects did not differ in their genetic polymorphism of the -308 nucleotide (P = 0.259). However, the relation of the tumor grade with the GA phenotype was statistically significant (P = 0.04). TNF-alpha mRNA concentrations were also significantly greater in the GA genotype than in the GG genotype (P = 0.022). The TNF-alpha serum levels of the GA genotype were significantly greater than those of the GG genotype for both patients and controls. However, patients with bladder tumor had significantly greater TNF-alpha serum levels than did the controls for both the GG and the GA genotypes (GG type, P = 0.001; GA type, P = 0.009).Conclusions. The genotype of the -308 nucleotide in the TNF-alpha promoter had a statistically significant effect on TNF-alpha production and was related to the bladder tumor grade. The GA polymorphism might be associated with a statistically significant increase in gene transcription. That the TNF-alpha serum levels were greater in the patients with bladder tumor compared with controls suggests that high TNF-alpha production is associated with bladder tumor development and that bladder tumors may secrete TNF-alpha. (C) 2004 Elsevier Inc.