Kostulas N, Markaki I, Kostulas V, Hillert J, Kostulas K
Department of Neurology, Neuro-Angiological Research Center, Karolinska Institutet at Karolinska University Hospital, Huddinge, Sweden.
Scand J Immunol. 2009 Nov;70(5):475-80. doi: 10.1111/j.1365-3083.2009.02323.x.
Inflammation is involved in the development of atherosclerosis. The CC chemokine receptor 5 (CCR5) initiates chemotaxis and modulates the inflammation secondary to atherosclerosis and related vascular diseases. The CCR5 Delta32 polymorphism influences the expression of CCR5 on the cell surface. The purpose of this study was to examine the effect of the Delta32 polymorphism in ischaemic cerebrovascular disease (ICVD). The CCR5 Delta32 polymorphism was genotyped in 1462 individuals: 562 ischaemic stroke (IS), 97 transient ischaemic attack (TIA) and in 803 healthy controls. All 659 ICVD patients were categorized according to the Trial of Org 10172 in Acute Stroke Treatment aetiological classification. The investigated subtypes were large artery atherosclerosis (LAA), cardioembolism (CE), small artery occlusion (SAO) and cryptogenic disease (CRYPT). Genotyping was performed with the TaqMan polymerase chain reaction. The Delta32 allele was less frequent in CE patients compared with LAA (OR, 0.4; 95% CI, 0.24-0.79; P = 0.008), SAO (OR, 0.5; 95% CI, 0.29-0.84; P = 0.01), CRYPT (OR, 0.5; 95% CI, 0.28-0.82; P = 0.008) and controls (OR, 0.5; 95% CI, 0.36-0.82; P = 0.002). Multiple logistic regression analysis showed that the Delta32 allele is associated with a lower risk for cardioembolic ICVD (OR 0.5; 95% CI, 0.28-0.75; P = 0.002) when compared with ICVD of other causes. The Delta32 polymorphism of CCR5 may differentiate cardioembolism from the remaining causes of ICVD.
炎症参与动脉粥样硬化的发展。C-C趋化因子受体5(CCR5)启动趋化作用,并调节动脉粥样硬化及相关血管疾病继发的炎症。CCR5 Delta32多态性影响CCR5在细胞表面的表达。本研究的目的是检测Delta32多态性在缺血性脑血管疾病(ICVD)中的作用。对1462名个体进行CCR5 Delta32多态性基因分型:562例缺血性中风(IS)、97例短暂性脑缺血发作(TIA)以及803名健康对照者。所有659例ICVD患者均根据急性中风治疗中Org 10172试验的病因分类进行归类。所研究的亚型包括大动脉粥样硬化(LAA)、心源性栓塞(CE)、小动脉闭塞(SAO)和隐源性疾病(CRYPT)。采用TaqMan聚合酶链反应进行基因分型。与LAA(比值比,0.4;95%可信区间为0.24 - 0.79;P = 0.008)、SAO(比值比,0.5;95%可信区间为0.29 - 0.84;P = 0.01)、CRYPT(比值比,0.5;95%可信区间为0.28 - 0.82;P = 0.008)以及对照组(比值比,0.5;95%可信区间为0.36 - 0.82;P = 0.002)相比,CE患者中Delta32等位基因的频率较低。多因素逻辑回归分析显示,与其他病因的ICVD相比,Delta32等位基因与心源性栓塞性ICVD的较低风险相关(比值比0.5;95%可信区间为0.28 - 0.75;P = 0.002)。CCR5的Delta32多态性可能将心源性栓塞与ICVD的其他病因区分开来。