细胞间黏附分子-1启动子甲基化水平与脑梗死的相关性

目的 评估细胞间黏附分子-1(Intercellular adhesion molecule-1,ICAM-1)基因启动子区甲基化水平与脑梗死的相关性。方法 对2017年9月-2018年9月于解放军第960医院就诊患者进行回顾性分析,根据诊断标准挑选152例脑梗死患者为病例组,同期于该院体检健康者 152 例为对照组,采用酶联免疫吸附法(Enzyme linked immunosorbent assay,ELISA)检测2组受试者外周血ICAM-1水平,使用荧光定量甲基化特异性聚合酶链反应(Quantitative Methylation Specific PCR,qMSP)法测定2组受试者ICAM-1甲基化程度。结果 病例组外周血ICAM-1水平显著高于对照组(T=20.27,P<0.001); 病例组ICAM-1基因甲基化程度显著低于对照组(Z=-3.158,P=0.002); 病例组亚组分析发现有吸烟史者甲基化程度更低(Z=-3.305,P=0.001); 2组ICAM-1甲基化程度均与ICAM-1水平呈显著负相关(病例组r=-0.756,P<0.001; 对照组r=-0.823,P<0.001)。结论 ICAM-1低甲基化通过促进ICAM-1的高表达,参与脑梗死的病理过程,可能通过调节基因表达水平来影响脑梗死的患病风险。ICAM-1启动子区甲基化程度升高可作为脑梗死的保护因素。

The correlation between methylation level of Intercellular Adhesion Factor-1(ICAM-1)promoter region and cerebral infarction

ObjectiveTo evaluate the correlation between methylation level of Intercellular Adhesion Factor-1(ICAM-1)promoter region and cerebral infarction.Methods From September, 2017 to September, 2018, 152 patients who suffered from cerebral infarction and admitted in 960 Hospital of PLA were selected as a case group for retrospective analysis with 152 physically healthy individuals chossen as a control group based on diagnostic criteria. The levels of ICAM-1 were measured in the peripheral blood in the two groups using an enzyme-linked immunosorbent assay(ELISA). The degree of methylation of ICAM-1 was determined using fluorescence quantitative methylation specific PCR(qMSP).Results The level of ICAM-1 identified in the patient group was significantly higher than that in the control group(T=20.27, P<0.001; 274.51±22.10 in case group, 220.93±23.95 in control group). The level of ICAM-1 gene methylation in patient group was significantly lower that in control group(Z=-3.158, P=0.002; 0.16(0.09,0.24)in case group, 0.19(0.12,0.31)in control group). Subgroup analysis showed that the methylation level of ICAM-1 was lower in patients with a history of smoking(Z=-3.305, P=0.001. There was a significant negative correlation between the methylation degree of ICAM-1 and the level of ICAM-1 in two groups(r=-0.756, P<0.001; r=-0.823, P<0.001).Conclusion Low methylation of ICAM-1 contributes to the pathological process ofcerebral infarction by promoting the high expression of ICAM-1, which may affect the risk of cerebral infarction by regulating gene expression levels. Elevated methylation in ICAM-1 promoter region can be used as a protective factor for cerebral infarction.