Staals Julie, Pieters Barbe M A, Knottnerus Iris L H, Rouhl Rob P W, van Oostenbrugge Robert J, Delanghe Joris R, Lodder Jan
Department of Neurology, University Hospital Maastricht, the Netherlands.
Curr Neurovasc Res. 2008 Aug;5(3):153-8. doi: 10.2174/156720208785425675.
Haptoglobin (Hp) 2-2 phenotype has been associated with peripheral and coronary artery disease and risk of vascular complications in diabetic patients, but any association of Hp polymorphism with cerebrovascular disease has not been explored so far. We aimed to study Hp polymorphism in a sample of 124 patients with a rather homogeneous type of cerebrovascular disease, namely first symptomatic lacunar stroke due to small vessel disease, in comparison with a large (n=918) control group. Hp phenotypes were determined using starch gel electrophoresis. Hp1 allele frequency was significantly higher in patients than in controls (0.480 vs. 0.395, p<0.05), mainly due to a lower Hp2-2 phenotype frequency (25.0 vs. 36.3 %; OR 0.59; 95%CI 0.38-0.90; p<0.05). This was even more pronounced in younger (<or=60 years) patients (Hp1 allele frequency 0.539). Concomitant asymptomatic lacunar lesions were present in 82 patients, extensive white matter lesions in 47 patients. The association between Hp1 and lacunar stroke suggests that Hp may serve different functions depending on the pathological processes in various types of vascular disease in different organs. The association between Hp1 and lacunar stroke may relate to blood-brain barrier dysfunction, to the association between hypertension and cerebral small vessel disease, or a special dependence of small vessel wall integrity on Hp2-2 related angiogenic potential. The presence of concomitant signs of cerebral small vessel disease weakened the association between Hp1 and lacunar stroke, which could reflect a difference in underlying vascular pathophysiology in which Hp phenotype may play a different role.
触珠蛋白（Hp）2-2表型与外周血管疾病、冠状动脉疾病以及糖尿病患者血管并发症的风险相关，但迄今为止尚未探讨Hp多态性与脑血管疾病之间的任何关联。我们旨在研究124例具有相当同质类型脑血管疾病（即因小血管疾病导致的首次有症状腔隙性卒中）患者样本中的Hp多态性，并与一个大的对照组（n=918）进行比较。使用淀粉凝胶电泳确定Hp表型。患者的Hp1等位基因频率显著高于对照组（0.480对0.395，p<0.05），主要是由于Hp2-2表型频率较低（25.0%对36.3%；OR 0.59；95%CI 0.38 - 0.90；p<0.05）。在年龄较小（≤60岁）的患者中这种情况更为明显（Hp1等位基因频率为0.539）。82例患者存在伴随的无症状腔隙性病变，47例患者存在广泛的白质病变。Hp1与腔隙性卒中之间的关联表明，根据不同器官各种类型血管疾病中的病理过程，Hp可能发挥不同的功能。Hp1与腔隙性卒中之间的关联可能与血脑屏障功能障碍、高血压与脑小血管疾病之间的关联，或小血管壁完整性对与Hp2-2相关的血管生成潜能的特殊依赖性有关。脑小血管疾病伴随体征的存在削弱了Hp1与腔隙性卒中之间的关联，这可能反映了潜在血管病理生理学的差异，其中Hp表型可能发挥不同的作用。
