肿瘤坏死因子微卫星多态性与慢性萎缩性胃炎和胃腺癌的相关性研究

目的 探讨中国湖北地区汉族人群中肿瘤坏死因子（TNF）d和TNFe微卫星多态性分布,分析其与慢性萎缩性胃炎和胃腺癌的相关性。方法 应用聚合酶链反应（PCR）结合变性聚丙烯酰胺凝胶高压电泳和硝酸银染色,对164例正常对照者、53例慢性萎缩性胃炎患者和56例胃腺癌患者的TNFd和TNFe微卫星进行分型,并将PCR产物克隆及测序鉴定。结果 TNFd微卫星检测到8个等位基因,TNFe检测到4个等位基因,其中一个新的等位基因经克隆及测序得以证实,并被Genebank收载（登录号AF315593）。统计分析显示,TNFd8和TNFe4等位基因呈现极其强烈的连锁不平衡。TNFd和TNFe等位基因频率在正常人群、慢性萎缩性胃炎和胃腺癌患者中的差异无显著意义,但胃腺癌患者中d2/d6基因型频率高于正常人群（P＝2．028）。d2/d6基因型与胃腺癌患者年龄、性别、分化程度和临床病理分期无关。结论 TNFd8/TNFe4单体型可能为中国人群所特有,d2/d6基因型与胃腺癌发病的易感性相关。

Association of tumor necrosis factor microsatellite polymorphism with chronic atrophic gastritis and gastric adenocarcinoma

OBJECTIVE: To investigate whether TNFd and TNFe microsatellite polymorphisms correlate with chronic atrophic gastritis and gastric adenocarcinoma in Chinese Han population. METHODS: In 164 healthy controls, 53 patients with chronic atrophic gastritis, and 56 patients with gastric adenocarcinoma, TNFd and TNFe microsatellite alleles were typed using PCR technique, followed by high-voltage denaturing PAGE, with silver staining. At the same time, the PCR products were cloned and sequenced. RESULTS: Fight alleles at the TNFd locus and four alleles at the TNFe locus were detected. A new allele was found and identified, its accession number of Genebank is AF315593. Statistical analysis showed that there existed a very strong linkage equilibrium between TNFd8 and TNFe4 allele. No difference was observed between patients and healthy controls in the distribution of alleles at the TNFd and TNFe loci (P > 0.05). The frequence of d2/d6 genotype was significantly higher in patients with gastric adenocarcinoma than in healthy individuals (P = 0.028). d2/d6 genotype wasn't related to age or gender or grade of differentiation or clinicopathologic stage in gastric adenocarcinoma. CONCLUSION: d8e4 haplotype appears to be specific of Chinese population. d2/d6 genotype is associated with the susceptibility to gastric adenocarcinoma.