COX基因多态性与缺血性卒中的相关性研究

Cyclooxygenase metabolic pathway-related gene polymorphisms and their relationship to the incidence of ischemic stroke

目的探讨环氧合酶(COX)代谢通路基因多态性及其与缺血性卒中发病率的关系.方法将2013年2月~2015年11月在德阳市人民医院和温州医科大学第三附属医院神经内科住院经头颅CT和MRI检查确诊的299例急性缺血性卒中患者,根据彩超结果分为颈动脉易损斑块组(VP)94例、稳定斑块组(SP)74例和无斑块组(NP)131例;同时再分为颈动脉内膜增厚组(IT)108例和非内膜增厚组(NT)191例.使用聚合酶链反应和质谱分析测定基因多态性,包括前列腺素合酶1 (PTGS1-rs1236913)、前列腺素H合酶2(PTGS2-rs689466)、血栓素A2合酶(TBXAS1-rs2267679、rs41708、rs194149)、前列腺素E合酶(PTGES2-rs647 8818)、环前列腺素合成酶(PTGIS-rs5602、rs5629).结果在易损斑块组和无斑块组之间TBXAS1-rs194149 GG基因型(P=0.0281),PTGIS-rs5602 CT基因型(P=0.0319)存在显著差异.内膜增厚组和非内膜增厚组之间PTGS2-rs689466 GG基因型(P=0.0216)显示显著差异.多元回归分析显示,PTGIS的AA基因型(P=0.0308,OR:0.275,95%CI:0.079~0.955)和PTGS2的AG+ GG基因型(P=0.0065,OR:2.162,95%CI:1.232~3.795)是内膜增厚的破坏性因素.结论 COX的单核苷酸多态性(SNP)与脑梗死的发病率存在相关性,PTGIS和PTGS2基因多态性与内膜增厚脑卒中患者相关.

Objective To investigate cyclooxygenase(COX) metabolic pathway-related gene polymorphisms and their relationship to the incidence of ischemic stroke in southern China. Methods Acute ischemic stroke patients(n=299) were divided into carotid vulnerable plaque group, stable plaque group, none plaque group, a carotid intima thickening group and none intima thickening group, according to the results of carotid B-mode ultrasonography. Genetic polymorphisms of prostaglandin H synthase 1(PTGS1—rs1236913), prostaglandin H synthase 2(PTGS2—rs689466), thromboxane A2 synthase(TBXAS1—rs2267679, rs41708, rs194149), prostaglandin E synthase(PTGES—rs6478818), prostacyclin synthase(PTGIS—rs5602, rs5629) were determined using polymerase chain reaction and mass spectrometry analysis. Results The distribution of TBXAS1—rs194149 GG genotype(P=0.0281), PTGIS—rs5602 CT genotype(P=0.0319) showed significant differences between the vulnerable plaque and none plaque groups. The distribution of PTGS2—rs689466 GG genotype(P=0.0216) showed significant differences between the intima thickening and none intima thickening groups. Multivariate logistic regression analysis showed the AA genotype of PTGIS(P=0.0308, OR: 0.275, 95%CI: 0.079-0.955) and the AG+GG genotype of PTGS2(P=0.0065, OR: 2.162, 95%CI: 1.232-3.795) were destructive factor for intima thickening. Conclusion The single nucleotide polymorphism(SNP) of COX genes link with the incidence of cerebral infarctions. The further studies show that PTGIS and PTGS2 genes polymorphism related with intima thickening in patients with stroke.