Sun Dandan, Sun Liping, Xu Qian, Gong Yuehua, Wang Honghu, Yang Jun, Yuan Yuan
Department of Tumor Etiology and Screening, Cancer Institute and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, China.
Key Laboratory of Cancer Etiology and Prevention, Liaoning Provincial Education Department, China Medical University, Shenyang 110001, China.
Int J Environ Res Public Health. 2016 Mar 4;13(3):278. doi: 10.3390/ijerph13030278.
The toll-like receptor 4 (TLR4)-myeloid differentiation factor 88 (MyD88)-dependent signaling pathway plays a role in the initiation and progression of coronary artery disease (CAD). We investigated SNP-SNP interactions between the TLR4 and MyD88 genes in CAD susceptibility and assessed whether the effects of such interactions were modified by confounding risk factors (hyperglycemia, hyperlipidemia and Helicobacter pylori (H. pylori) infection). Participants with CAD (n = 424) and controls (n = 424) without CAD were enrolled. Polymerase chain restriction-restriction fragment length polymorphism was performed on genomic DNA to detect polymorphisms in TLR4 (rs10116253, rs10983755, and rs11536889) and MyD88 (rs7744). H. pylori infections were evaluated by enzyme-linked immunosorbent assays, and the cardiovascular risk factors for each subject were evaluated clinically. The significant interaction between TLR4 rs11536889 and MyD88 rs7744 was associated with an increased CAD risk (p value for interaction = 0.024). In conditions of hyperglycemia, the interaction effect was strengthened between TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.004). In hyperlipidemic participants, the interaction strength was also enhanced for TLR4 rs11536889 and MyD88 rs7744 (p value for interaction = 0.006). Thus, the novel interaction between TLR4 rs11536889 and MyD88 rs7744 was related with an increased risk of CAD, that could be strengthened by the presence of hyperglycemia or hyperlipidemia.
Toll样受体4（TLR4）-髓样分化因子88（MyD88）依赖性信号通路在冠状动脉疾病（CAD）的发生和发展中起作用。我们研究了CAD易感性中TLR4和MyD88基因之间的单核苷酸多态性（SNP）-SNP相互作用，并评估了这些相互作用的影响是否会因混杂风险因素（高血糖、高脂血症和幽门螺杆菌（H. pylori）感染）而改变。纳入了424例CAD患者和424例无CAD的对照者。对基因组DNA进行聚合酶链反应-限制性片段长度多态性分析，以检测TLR4（rs10116253、rs10983755和rs11536889）和MyD88（rs7744）的多态性。通过酶联免疫吸附试验评估H. pylori感染情况，并对每个受试者的心血管危险因素进行临床评估。TLR4 rs11536889和MyD88 rs7744之间的显著相互作用与CAD风险增加相关（相互作用的p值 = 0.024）。在高血糖情况下，TLR4 rs11536889和MyD88 rs7744之间的相互作用效应增强（相互作用的p值 = 0.004）。在高脂血症参与者中，TLR4 rs11536889和MyD88 rs7744的相互作用强度也增强（相互作用的p值 = 0.006）。因此，TLR4 rs11536889和MyD88 rs7744之间的新型相互作用与CAD风险增加有关，高血糖或高脂血症的存在可增强这种作用。
