肿瘤坏死因子-α基因多态性与恶性肿瘤糖代谢异常的关系

Correlation between tumor necrosis factor-α single nucleotide polymorphisms and abnormal glucose metabolism in patients with malignant tumor

目的探讨肿瘤坏死因子-α（TNF-α）基因启动子区-238、-308位点基因多态性与恶性肿瘤糖代谢异常的关系。方法新乡医学院第一附属医院2013年4月至2014年5月经病理诊断确诊的恶性肿瘤患者根据口服葡萄糖耐量试验分为肿瘤且糖耐量正常患者（糖耐量正常组）、肿瘤合并糖耐量受损患者（糖耐量受损组）和肿瘤合并糖尿病患者（糖尿病组）,各组按照入院顺序随机抽取40例作为观察对象;另外,在知情同意的原则下随机选取40例体检健康者作为健康对照组。采用聚合酶链反应-限制性片断长度多态性分析法检测正常糖耐量组、糖耐量受损组、糖尿病组患者和健康对照组的TNF-α基因启动子-238、-308多态性,确定其基因型和等位基因频率的分布。结果糖耐量正常组患者的GA＋AA基因型频率与健康对照组比较差异无统计学意义（χ2=5.871,P〉0.05）。糖耐量受损组和糖尿病组患者的GA＋AA基因型频率高于健康对照组和糖耐量正常组（χ2=7.211、25.621,P〈0.05;χ2=5.267、18.015,P〈0.05）。糖尿病组患者的GA＋AA基因型频率与糖耐量受损组比较差异无统计学意义（χ2=4.236,P〉0.05）。糖耐量正常组和糖耐量受损组患者的TNF-α-308 A等位基因频率与健康对照组比较差异无统计学意义（χ2=2.137、3.215,P〉0.05）。糖尿病组患者的TNF-α-308 A等位基因频率显著高于健康对照组和糖耐量正常组（χ2=8.469、24.430,P〈0.05）,且显著高于糖耐量受损组（χ2=3.625,P〈0.05）。健康对照组仅1例出现AA基因型,糖耐量正常组、糖耐量受损组和糖尿病组患者中均未出现AA基因型,TNF-α-238基因型和A等位基因频率分布在各组间比较差异无统计学意义（χ^2=3.472、2.894,P〉0.05）。结论恶性肿瘤糖代谢异常与TNF-α-308基因的多态性有关。

Objective To investigate the correlation between single nucleotide polymorphisms of tumor necrosis factor- gene promotor-238 ,-308 and abnormal glucose metabolism in the patients with malignant tumor. Methods The patients with malignant tumor were selected in the First Affiliated Hospital of Xinxiang Medical University from April 2013 to May 2014. The patients were divided into normal glucose tolerance group, tumor with impaired glucose tolerance group and tumor with diabetes group according to the tolerance test ,40 cases in each group. Forty healthy persons were selected as healthy con- trol group randomly under the principle of informed consent. The polymorphisms at position-238 ,-308 of the promoter of TNF- c~ gene were determined by polymerase chain reaction-restriction fragment length polymorphisms analysis in the eaeh group, in order to confirm the genotype and the distribution of the allele frequency. Results There was no significant difference in the frequency of AA ＋ GA genotype between the normal glucose tolerance group and the healthy control group（x2 = 5. 871 ,P 〉 0. 05 ）. The frequency of AA ＋ GA genotype in tumor with impaired glucose tolerance group and tumor with diabetes group was higher than that in healthy control group and normal glucose tolerance group （X2 = 7.211,25. 621, P 〈 0. 05 ;X2 = 5. 267, 18. 015, P 〈 0.05 ）. There was no significant difference in the frequency of AA ＋ GA genotype between impaired glucose toler- ance group and tumor with diabetes group （X2 =4. 236, P 〉 0.05）. Compared with the healthy normal group, there was no sig- nificant difference in the frequency of TNF-α-308A allele in normal glucose tolerance group and tumor with impaired glucose tolerance group（x2 = 2. 137,3. 215 ;P 〉 0.05 ）. The TNF-α-308A allele frequency in the diabetes group was significantly high- er than that in the healthy control group and the normal glucose tolerance group and the impaired glucose tolerance group（xz = 8. 469,24. 430,3. 625 ; P 〈 0.05 ）. Only one ease of AA genotype was found in the healthy control group, normal glucose toler- ance, while it was not expressed in normal glucose tolerance group, impaired glueose tolerance group and diabetes group. The difference was not statistically significant in the TNF-α-238 genotype and AA allele frequency among the groups （X2 = 3. 472, 2. 894 ;P 〉 0.05 ）. Conclusion The abnormality of glucose metabolism in malignant tumor is related to the polymorphism of TNF-α-308 gene