【摘要】 目的　探讨中国湖北地区汉族人群中肿瘤坏死因子 (TNF)a、TNFb和TNFc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PCR结合变性聚丙烯酰胺凝胶高压电泳和AgNO3 染色 ,对 16 4例健康者、5 3例慢性萎缩性胃炎和 5 6例胃腺癌患者的TNFa、TNFb和TNFc微卫星进行分型 ,并将PCR产物克隆及测序鉴定。结果　慢性萎缩性胃炎中的TNFa10基因频率为19 .81% ,显著高于正常人中的 11.84 % (P =0 .0 4 )。进一步分析显示TNFa10等位基因与患者的年龄、性别、胃黏膜萎缩程度、肠上皮化生等无关。TNFa6b5c1单倍体纯合子在胃腺癌中的频率为 1.79% ,显著低于正常人中的 15 .85 % (P =0 .0 0 6 )。克隆测序发现 ,相同TNFa等位基因包含的 (AC/GT)重复序列拷贝数与国外文献报道中不一致。结论　TNFa等位基因的定义内涵尚需进一步确定。TNFa10等位基因与慢性萎缩性胃炎的易感性相关 ,TNFa6b5c1单倍体纯合子在慢性萎缩性胃炎至胃腺癌移行过程中发挥其抵抗作用更多还原

【Abstract】 Objective To investigate whether tumor necrosis factor (TNF)a, TNFb and TNFc microsatellite polymorphisms correlate with chronic atrophic gastritis and gastric adenocarcinoma in Chinese Han population. Methods TNFa, TNFb and TNFc microsatellite alleles in 164 healthy subjects, 53 patients with chronic atrophic gastritis and 56 patients with gastric adenocarcinoma were typed using PCR technique combined with High Voltage denaturing PAGE and silver staining. At the same time, the PCR products were cloned and sequenced. Results The frequency of TNFa10 allele was significantly higher in patients with chronic atrophic gastritis than in healthy individuals ( 19.81% vs. 11.89% , P = 0.04 ). However it was not related to age, gender, degree of atrophy or intestinal metaplasia in patients with chronic atrophic gastritis. The frequency of TNFa6b5c1 haplotype homozygote was significantly lower in patients with gastric adenocarcinoma than in healthy individuals ( 1.79% vs. 15.85% , P = 0.006 ). The sequence result revealed that the copy number of dinucleiotide repeating within the same TNFa allele was not consistent with that in the reports from Western countries. Conclusions It should be more accurate and clear to define TNFa alleles. TNFa10 allele is associated with the susceptibility to chronic atrophic gastritis. TNFa6b5c1 haplotype homozygote is negatively associated with gastric adenocarcinoma and thus may play a resistant role in the shifting process from chronic atrophic gastritis to gastric adenocarcinoma.更多还原