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

 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。

Expression of IL-1α and TNF-α modified by Toll-like receptor 4 genetic polymorphism is associated with colorectal carcinoma

AIM: To investigate the association of D299G, T399I and A896G polymorphisms of Toll-like receptor 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 associated 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 individuals 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.