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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 1 64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AF3 1 5593 )。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 =0 .0 2 8)。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。
Objective To investigate the distribution of tumor necrosis factor (TNF) d and TNFe microsatellite polymorphisms in Chinese Han population in Hubei Province, China, and to analyze their correlation with chronic atrophic gastritis and gastric adenocarcinoma. Methods Polymerase chain reaction (PCR) combined with denaturing polyacrylamide gel electrophoresis and silver nitrate staining were used to detect the polymorphisms of TNFd and TNFe in 64 normal controls, 53 patients with chronic atrophic gastritis and 56 patients with gastric adenocarcinoma The PCR products were cloned and sequenced. Results Eight alleles were detected in the TNFα microsatellite and four alleles were detected in the TNFe. One of the new alleles was confirmed by cloning and sequencing and was deposited by Genebank (accession number AF3 1 5593). Statistical analysis showed that TNFd8 and TNFe4 alleles showed extremely strong linkage disequilibrium. There was no significant difference in the frequency of TNFα and TNFα alleles among normal population, chronic atrophic gastritis and gastric adenocarcinoma, but the frequency of d2 / d6 genotype in patients with gastric adenocarcinoma was higher than that in normal population (P = 0.028) . The genotype of d2 / d6 was not related to the age, sex, differentiation and clinicopathologic stage of gastric adenocarcinoma. Conclusion The haplotypes of TNFd8 / TNFe4 may be unique to the Chinese population. The d2 / d6 genotype is associated with the susceptibility to gastric adenocarcinoma.