IL-1β血清水平及IL-1B和IL-1受体拮抗剂基因多态性与胃癌关系探讨

目的 探讨白细胞介素(IL)-1β血清水平及IL-1B和IL-1RN基因多态性与胃癌及幽门螺杆菌(Hp)感染胃癌发生发展的相关性.方法 以酶联免疫吸附试验(ELISA)测定IL-1β血清水平及抗Hp抗体IgG、IgM和IgA浓度;采用基因芯片技术检测260例胃癌患者和284例不相关联的健康对照人群中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).结果 胃癌组IL-1β血清水平[(802±148) ng/L]显著高于对照组[(501±125) ng/L],P<0.01;胃癌组Hp感染率明显高于对照组[P<0.001, 相对危险度(OR)=2.59].胃癌组IL-1B-31TT基因型频率明显高于对照组(P<0.01,OR=1.95);胃癌组IL-1B-511TT基因型频率明显高于对照组(P<0.05,OR=1.62);Hp阳性(Hp+)胃癌组-511TT基因型频率明显高于Hp阴性(Hp-)胃癌(P<0.05,OR= 2.00);胃癌组T-T单体型频率显著高于对照组(χ2=4.45,P<0.05).不论在胃癌组还是在Hp+胃癌组,携带IL-1B-31T或-511T等位基因者血清IL-1β水平均高于其相应CC基因型携带者,且IL-1B-31T、-511T携带者在Hp+胃癌组较Hp-胃癌组的IL-1β水平显著增高(P<0.001).未见IL-1RN基因型及其他IL-1B基因型与胃癌或Hp+胃癌有显著相关性.结论 IL-1B-31TT基因型与胃癌易感性相关;IL-1B-511TT基因型与胃癌特别是Hp+胃癌易感性相关.IL-1B-31T/-511T等位基因均与IL-1β血清水平显著相关(P<0.001).T-T单体型可能是胃癌的遗传易感因素.

Serum level and genotype of interleukin-1β or interleukin-1 receptor antagonist in patients with gastric cancer

Objective To investigate the relationships of the serum level of interleukin-1β(IL-1β), the single nucleotide polymorphism(SNP) of IL-1B and interleukin-1 receptor antagonist (IL-1RN) genes with the gastric cancer or the gastric cancer infected by Helicobacter pylori(Hp). Methods The SNP of the IL-1B(-31C/T and -511C/T) was determined by gene chip and the variable number of tandem repeat(VNTR) of IL-1RN were detected by agarose gel electrophoresis. The sera level of IL-1β and the concentrations of IgG, IgM and IgA of Hp antibodies were measured by ELISA. Results The serum level of IL-1β increased significantly in patients with gastric cancer than that in control group(P<0.001). Hp infection was detected in 69.2% of 260 patients and 46.5% of 284 controls[P<0.001, odds ratio (OR)=2.59]. Frequency of genotype IL-1B-31TT or IL-1B-511TT in patients with gastric cancer were significantly higher than that in healthy controls (P<0.01, OR=1.95; P<0.05, OR=1.62), respectively. Frequency in Hp+ gastric cancer group was higher than that in Hp- group (P<0.05, OR= 2.00), and frequency of haplotype T-T in patients group was significantly higher than that in healthy control(χ2=4.45, P<0.05). The serum level [(802±148) ng/L] of IL-1β of the gastric cancer group was significantly higher than that of the control group [ (501±125) ng/L, P<0.01]. The serum level of IL-1β in patients with -31T or -511T allele was (845±156) ng/L or (871±148) ng/L, significantly higher than that without -31T [(555±116) ng/L] and -511T allele [(581±128) ng/L]. Furthermore, The serum level of IL-1β in Hp+ group with T allele were significantly higher than that in Hp- group (P<0.001). There was no association of IL-1RN gene and other IL-1B gene with gastric cancer or Hp+ gastric cancer. Conclusion IL-1B-31TT genotype was related to gastric cancer. IL-1B-511TT genotype was related to gastric cancer or with Hp+ gastric cancer. Both IL-1B-31T and -511T are associated with IL-1B gene. The haplotype T-T may be the genetic susceptible factor to gastric cancer.