Objective To identify the relationship between variant rs3662C＞A in the gene of p21-activated kinase 2 (PAK2) and risk of stroke as well as prognosis, and to explore the effect of rs3662C＞A on the transcriptional activity of PAK2 gene. Methods In a multi-center case-control study including 733 cerebral atherothrombotic stroke, 488 lacunar infarction, 435 intracerebral hemorrhage and 1 727 healthy controls, the relationship between variant and risk of three stroke subtypes was examined using the multivariate logistic regression model. The stroke patients were prospectively followed up for a median of 4.5 years, and the relationship between rs3662 and cardiovascular events as well as mortality was analyzed using the Cox proportional-hazards model. The effect of rs3662C＞A on the transcriptional activity of PAK2 gene was examined using the luciferase reporter assays. Results The rs3662A allele was associated with a decreased risk of atherosclerotic stroke as compared with rs3662CC genotype, and odds ratio was 0.67 (95% CI: 0.47~0.95,P＜0.05) in a dominant genetic model. This relationship had sex-specific difference and was significant incline to male. During the follow-up, atherosclerotic stroke patients carrying with rs3662A allele had a significantly higher risk of cardio-cerebrovascular events and cardiovascular mortality; hazards ratio was respectively 1.84 (95% CI: 1.16~2.92,P＜0.05) and 2.06 (95% CI:1.05~4.04,P＜0.05). The rs3662C significantly reduced the luciferase activity by 79% (P＜0.01). Conclusions The carriers with rs3662A allele of PAK2 gene have a reduced risk for atherosclerotic stroke but a worse prognosis. It is found that rs3662A affects the PAK2 expression level.

目的:探究冠状动脉CT血管成像(CCTA)技术对冠状动脉易损斑块和主要不良心血管事件风险预测的评估价值.方法:连续入选2016年4月至2018年5月在中国医学科学院阜外医院门诊因冠状动脉粥样硬化性心脏病(冠心病)或疑似冠心病进行CCTA检查且显示冠状动脉斑块阳性的患者517例,其中男性327例,女性190例.根据CCTA检查结果将患者分为钙化斑块组(222例)和混合斑块组(295例),应用128排螺旋CT进行冠状动脉图像的重建与分析.通过电话、查阅病历以及联系主管医师等方式随访主要不良心血管事件发生情况,包括心原性猝死、急性心肌梗死、不稳定性心绞痛、冠状动脉旁路移植术、冠状动脉支架置入术、急性心力衰竭.采用多因素Logistic回归模型分析影响斑块易损性的相关危险因素,计算OR和95％CI;采用Cox生存回归模型分析冠状动脉斑块特征对心血管终点事件的影响,计算HR和95％CI.结果:本研究517例患者的平均年龄为(57.9±8.4)岁,男性占63.2％.混合斑块组患者的血清总胆固醇、低密度脂蛋白胆固醇显著高于钙化斑块组(P<0.05),而高密度脂蛋白胆固醇显著低于钙化斑块组(P<0.05).混合斑块组的脂质成分负荷和纤维成分负荷显著高于钙化斑块组(P=0.01),造成的血管狭窄率显著大于钙化斑块组(P=0.02).多因素Logistic回归模型分析发现脂质成分高负荷的斑块发生斑块易损性的风险增加(OR=2.30,95％CI:1.45～3.64;P<0.001),而纤维成分高负荷的斑块与斑块易损性风险呈负相关(OR=0.73,95％CI:0.38～0.91;P<0.001).平均随访15个月(范围3～29个月),所有患者随访结束时,有42例(8.1％)发生主要不良心血管事件.采用多因素Cox回归风险模型分析发现纤维成分高负荷的斑块发生主要不良心血管事件的风险增加(HR=3.33,95％CI:1.24～8.98;P=0.02),钙化高负荷的斑块也增加主要不良心血管事件的发生风险(HR=4.29,95％CI:1.47～12.46;P=0.01).结论:通过CCTA技术检测冠状动脉斑块总体积、脂质成分负荷、纤维成分负荷、钙化成分负荷等指标在冠状动脉斑块易损性和主要不良心血管事件发生风险的评价中具有应用价值,尚需多临床中心、大样本、前瞻性队列研究的循证依据.