IL-1基因多态性与胃腺癌发生的关系

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目的:探讨白介素-1B(IL-1B)和白细胞介素-1RN(IL-1RN)基因多态性与胃腺癌及幽门螺杆菌(Hp)感染胃腺癌发生发展的相关性。方法:采用基因芯片技术检测130例胃腺癌患者和142例健康对照人群中IL-1B-31C/T、-511C/T位点单核苷酸多态性(SNP);以琼脂糖凝胶电泳检测IL-1RN基因多态性(VNTR),同时应用酶联免疫吸附试验(ELISA)测定了其血清中HP-IgG/IgM/IgA型抗体浓度。结果:感染Hp阳性率胃腺癌明显高于对照组(P=0.007,OR=2.53)。IL-1B-31TT频率,胃腺癌组明显高于对照组(P<0.05,OR=2.16),在低分化胃腺癌组明显高于高分化胃腺癌组(P<0.05,OR=6.55)。IL-1B-511TT基因型频率在胃腺癌组明显高于对照组(P<0.05,OR=1.81);在Hp阳性胃腺癌组-511TT基因型及T等位基因频率明显高于Hp阴性胃腺癌(P<0.05,OR=2.25及P<0.05,OR=1.78)。胃腺癌组T-T单体型频率显著高于对照组(χ2=4.56,P<0.05)。未见IL-1RN基因及IL-1B其他位点的SNP与胃腺癌组或Hp阳性胃腺癌组有显著相关性。结论:IL-1B-31TT基因型与胃腺癌特别是低分化胃腺癌易感性相关,IL-1B-511TT基因型与胃腺癌或感染Hp的胃腺癌易感性相关。T-T单体型可能是胃腺癌的遗传易感因素。 Objective: To investigate the association between interleukin-1B (IL-1B) and interleukin-1RN (IL-1RN) gene polymorphisms and the development of gastric adenocarcinoma and Helicobacter pylori (Hp)-infected gastric adenocarcinoma. METHODS: Single nucleotide polymorphisms (SNPs) of IL-1B-31C/T and -511C/T sites in 130 patients with gastric adenocarcinoma and 142 healthy controls were detected by gene chip technique; agarose gel electrophoresis The IL-1RN gene polymorphism (VNTR) was detected, and the concentration of HP-IgG/IgM/IgA antibodies in the serum was determined using an enzyme-linked immunosorbent assay (ELISA). Results: Gastric adenocarcinoma with a positive rate of Hp infection was significantly higher than that of the control group (P=0.007, OR=2.53). The frequency of IL-1B-31TT in the gastric adenocarcinoma group was significantly higher than that in the control group (P<0.05, OR=2.16), and it was significantly higher in the poorly differentiated gastric adenocarcinoma group than in the well-differentiated gastric adenocarcinoma group (P<0.05, OR=6.55). The frequency of IL-1B-511TT genotype was significantly higher in the gastric adenocarcinoma group than in the control group (P<0.05, OR=1.81); the frequency of the -511TT genotype and T allele in the Hp-positive gastric adenocarcinoma group was significantly higher than that of the Hp-negative gastric adenocarcinoma (P<0.05, OR=2.25 and P<0.05, OR=1.78). The frequency of T-T haplotype in the gastric adenocarcinoma group was significantly higher than that in the control group (χ2=4.56, P<0.05). No significant associations were found between IL-1RN gene and other sites of IL-1B SNP with gastric adenocarcinoma or Hp-positive gastric adenocarcinoma. Conclusion: IL-1B-31TT genotype is associated with the susceptibility of gastric adenocarcinoma, especially poorly differentiated gastric adenocarcinoma. The IL-1B-511TT genotype is associated with the susceptibility of gastric adenocarcinoma or gastric adenocarcinoma infected with Hp. The T-T haplotype may be a genetic susceptibility factor for gastric adenocarcinoma.
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