Yi Xingyang, Lin Jing, Luo Hua, Wang Chun, Liu Yingying
Department of Neurology, People's Hospital of Deyang City, Deyang, Sichuan, China.
Department of Neurology, the Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
PLoS One. 2017 Jul 12;12(7):e0180704. doi: 10.1371/journal.pone.0180704. eCollection 2017.
Eicosanoids may play a role in ischemic stroke. However, the associations of variants in cyclooxygenase (COX) pathway genes and interaction among these variants with carotid plaque vulnerability are not fully understood. In present study, twelve variants in COX pathway genes were examined using matrix-assisted laser desorption ionization time-of-flight mass spectrometry method in 396 patients with ischemic stroke and 291 controls. Platelet aggregation, platelet-leukocyte aggregates, and urine 11-dehydrothromboxane B2 (11-dTxB2) were also measured. According to the results of carotid high-resolution B-mode ultrasound, the patients were stratified into the following groups [i.e., non-carotid plaque and carotid plaque. The carotid plaque was further classified into subgroups of echolucent plaque (ELP) and echogenic plaque (EGP)]. Additionally, gene-gene interactions were analyzed to assess whether there was any interactive role for assessed variants in affecting carotid plaque vulnerability, platelet activation and 11-dTxB2 levels. There were no significant differences in the frequencies of genotypes of the twelve variants between patients and controls. Among 396 patients, 294 cases (74.2%) had carotid plaques (106 had ELP, 188 had EGP). Frequency of PTGS2 rs20417CC, TXAS1 rs2267679TT, TXAS1 rs41708TT, PTGIS rs5602CC, and TXA2R rs1131882TT genotype was significantly higher in patients with plaque compared with patients without plaque, or in patients with ELP compared with patients with EGP. 11-dTxB2 levels, platelet aggregation and platelet-leukocyte aggregates were significantly higher in patients with ELP compared with patients without plaque or with EGP. Multivariate logistic regression analysis revealed that PTGS2 rs20417CC, TXA2R rs1131882TT, and high-risk interaction among variants in PTGS2 rs20417, TXA2R rs1131882 and TXAS1 rs41708 were independently associated with the risk of ELP after adjusting for confounding variables. The variants in COX pathway genes and the high-risk interactions among variants in PTGS2 rs20417, TXA2R rs1131882 and TXAS1 rs41708 were associated with high 11-dTxB2 and platelet activation, and independently associated with the risk of carotid plaque vulnerability. These variants might be potential markers for plaque instability.
类花生酸可能在缺血性卒中中发挥作用。然而，环氧化酶（COX）途径基因变异及其相互作用与颈动脉斑块易损性之间的关联尚未完全明确。在本研究中，采用基质辅助激光解吸电离飞行时间质谱法检测了396例缺血性卒中患者和291例对照者COX途径基因中的12个变异。同时还检测了血小板聚集、血小板-白细胞聚集体以及尿11-脱氢血栓素B2（11-dTxB2）。根据颈动脉高分辨率B型超声检查结果，将患者分为以下几组[即无颈动脉斑块组和颈动脉斑块组。颈动脉斑块进一步分为低回声斑块（ELP）和高回声斑块（EGP）亚组]。此外，分析基因-基因相互作用以评估所检测的变异在影响颈动脉斑块易损性、血小板活化和11-dTxB2水平方面是否存在交互作用。患者和对照者中12个变异的基因型频率无显著差异。在396例患者中，294例（74.2%）有颈动脉斑块（106例为ELP，188例为EGP）。与无斑块患者相比，或与EGP患者相比，有斑块患者中PTGS2 rs20417CC、TXAS1 rs2267679TT、TXAS1 rs41708TT、PTGIS rs5602CC和TXA2R rs1131882TT基因型的频率显著更高。与无斑块或EGP患者相比，ELP患者的11-dTxB2水平、血小板聚集和血小板-白细胞聚集体显著更高。多因素逻辑回归分析显示，在调整混杂变量后，PTGS2 rs20417CC、TXA2R rs1131882TT以及PTGS2 rs20417、TXA2R rs1131882和TXAS1 rs41708变异之间的高危相互作用与ELP风险独立相关。COX途径基因变异以及PTGS2 rs20417、TXA2R rs1131882和TXAS1 rs41708变异之间的高危相互作用与高11-dTxB2和血小板活化相关，并与颈动脉斑块易损性风险独立相关。这些变异可能是斑块不稳定的潜在标志物。
