TLR4基因T399I多态性通过调节IL-1α和TNF-α表达影响结直肠癌的发生

摘要

目的:研究Toll样受体4(TLR4)多态性与结直肠癌相关性及可能的机制.方法:聚合酶链反应-限制性片段长度多态性 (PCR-RFLP)检测268名结直肠癌患者和268名健康对照个体TLR4 A896G、D299G和T399I多态性位点基因型,ELISA方法检测结直肠癌组织匀浆中白细胞介素1α(IL-1α)、IL-8、转化生长因子β(TGF-β)和肿瘤坏死因子α(TNF-α)蛋白水平.结果:TLR4 A896G和D299G多态性基因型在病例-对照组中频率无显著性差异,T399I CT合并TT基因型显著增加结直肠癌的患病风险,而携带T399I T等位基因的个体患病风险是C等位基因个体的1.843倍;IL-1α和TNF-α浓度在T399I CT合并TT基因型个体结直肠癌组织中的表达显著高于T399I CC基因型个体.结论:TLR4 T399I可能通过调控结直肠癌组织中IL-1α和TNF-α的表达促进结直肠癌发生.%AIM: To investigate the association of D299G, T399I and A896G polymorphisms of Toll -like recep-tor 4 (TLR4) and colorectal carcinoma (CRC). METHODS: The genotypes of these 3 loci among 268 patients with CRC and 268 healthy controls were determined by polymerase chain reaction - restriction fragment lengthy polymorphism ( PCR -RFLP). The protein levels of IL - 1α, IL -8, TGF - β and TNF -α in the homogenate of CRC biopsies were measured by enzyme - linked immunosorbent assay ( ELISA). RESULTS: No significant difference of the genotype frequencies of TLR4 A896G and D299G between the cases and the controls was observed. CT combined TT genotype of T399I was significantly as-sociated with increased CRC risk. The individuals with the T allele of T399I showed a 1. 843 -fold increase in CRC risk as compared with the C allele. The concentrations of IL - 1α and TNF - α in CRC biopsies were significantly elevated in the in-dividuals with the genotype of T399I CT combined with TT as compared with the genotype of CC. CONCLUSION: TLR4 T399I promotes the development of CRC by modifying the expression of IL - 1α and TNF - α in CRC tissues.