广西壮族人群TNF-α基因多态性及其表达与原发性肝细胞癌的相关性研究

摘要

目的：探讨肿瘤坏死因子-α（TNF-α）-238/-3082个位点的基因单核苷酸多态性（SNP）及血清TNF-α水平与广西壮族人群原发性肝细胞癌（HCC）的关系及其临床意义。方法将175名研究对象分为HCC组102例和正常对照组73名，采用双抗体夹心酶联免疫吸附试验（ELISA）和聚合酶链反应-限制性内切酶长度多态性（PCR-RFLP）技术检测血清TNF-α水平并对TNF-α-308/-2382个位点基因多态性进行分型。结果 HCC组血清TNF-α水平显著高于正常对照组（P<0.01），携带TNF-α-308 GA+AA基因型的个体血清TNF-α水平表达高于携带TNF-α-308 GG基因型个体（P<0.01）。HCC组TNF-α-308位点的基因型和等位基因频率均高于正常对照组（P<0.05），TNF-α-238位点的基因型和等位基因频率在HCC组和正常对照组中的分布差异均无统计学意义（P>0.05）。携带TNF-α-308位点GA或AA基因型的个体与携带GG基因型的个体相比发生肝癌的风险更高[比值比OR=3.556，95%可信区间（CI）1.581~7.994]，携带TNF-α-308A等位基因的个体患HCC的风险是携带G等位基因个体的3.153倍（OR=3.153，95%CI 1.465~6.784）。结论 HCC患者的血清TNF-α水平高于正常对照组。TNF-α-308位点多态性与血清TNF-α水平有关。TNF-α-308位点多态性可能与广西地区壮族人群HCC的遗传易感性有关。%Objective To investigate the correlations of tumor necrosis factor-alpha(TNF-α) -238/-308 single nucleotide polymorphism(SNP) and serum TNF-α levels with primary hepatocellular carcinoma (HCC) in Guangxi Zhuang population. Methods A total of 175 subjects were classified into primary HCC group(102 cases) and healthy control group(73 cases). Serum TNF-α levels and the genotypes of TNF-α-238/-308 SNP were determined by double antibody sandwich enzyme-linked immunosorbent assay(ELISA) and polymerase chain reaction(PCR)-restriction fragment length polymorphism(RFLP). Results Serum TNF-α levels in primary HCC group were higher than those in healthy control group(P<0.01). For the genotype of TNF-α-308, serum TNF-α level of GA+AA genotype was higher than that of GG genotype(P<0.01). The genotype and allele frequencies of TNF-α-308 in primary HCC group were higher than those in healthy control group(P<0.05). The genotype and allele frequencies of TNF-α-238 in primary HCC group and healthy control group had no statistical significance(P>0.05). The risk of primary HCC was higher in TNF-α-308 GA or AA genotype than that in TNF-α-308 GG genotype [odds ratio(OR)=3.556,95% confidence interval(CI)1.581-7.994]. The risk in TNF-α-308 A allele was 3.153 times higher than that in TNF-α-308 G allele (OR=3.153,95%CI 1.465-6.784). Conclusions Serum TNF-α levels in primary HCC group are higher than those in healthy control group. TNF-α-308 SNP are correlated to serum TNF-α levels. TNF-α-308 SNP may be correlated to the genetic susceptibility of primary HCC in Guangxi Zhuang population.