Neurology Department, Versailles Hospital and Versailles Saint-Quentin-en-Yvelines University, Versailles, France.
Ann Neurol. 2010 Apr;67(4):508-15. doi: 10.1002/ana.21922.
Intracranial arterial dolichoectasia (IADE), also called dilatative arteriopathy of the brain, is defined as an increase in length and diameter of intracranial arteries. Abdominal aortic aneurysm and ectasia of coronary arteries have been reported in association with IADE. In both conditions, a dysfunction of matrix metalloproteinases (MMP)-2, -3, and -9 have been found. Our aim was to investigate these MMP pathways in stroke patients with IADE.
Five hundred ten Caucasians patients with brain infarction were consecutively recruited at 12 centers. The diagnosis of IADE was made by consensus between 2 neurologists based on magnetic resonance imaging scans. Determination of MMP-2, -3, and -9 plasma levels was centralized in 1 laboratory. Because we found a threshold effect of MMP-3 plasma levels with the risk of IADE, determination of the MMP-3 5A/6A polymorphism was carried out.
IADE was identified in 12% of stroke patients. There was no association of IADE with mean MMP-2, -3, and -9 plasma levels. After categorization of MMP plasma levels into tertiles, we found a higher risk of IADE with the lowest MMP-3 tertile (adjusted odds ratio [OR], 2.48; 95% confidence interval [CI], 1.17-5.23). In genotype analysis, there was a significant additive effect of the 5A allele on the risk of IADE, with an adjusted OR of 1.62 (95% CI, 1.03-2.55).
In this cohort of stroke patients of Caucasian ancestry, IADE was associated with low MMP-3 plasma levels and with the 5A/6A polymorphism of the promoter region of MMP-3. These results suggest that MMP-3 may play a role in IADE.
颅内动脉迂曲扩张症（IADE），也称为脑扩张性动脉病，定义为颅内动脉长度和直径增加。已有报道称，腹主动脉瘤和冠状动脉扩张与 IADE 相关。在这两种情况下，均发现基质金属蛋白酶（MMP）-2、-3 和 -9 功能障碍。我们的目的是研究 IADE 脑卒中患者的这些 MMP 途径。
在 12 个中心连续招募了 510 名患有脑梗死的白种人患者。IADE 的诊断由 2 位神经病学家根据磁共振成像扫描结果达成共识。MMP-2、-3 和 -9 的血浆水平测定在 1 个实验室集中进行。因为我们发现 MMP-3 血浆水平存在与 IADE 风险的阈值效应，所以进行了 MMP-3 5A/6A 多态性测定。
12%的脑卒中患者存在 IADE。IADE 与 MMP-2、-3 和 -9 的平均血浆水平无关。将 MMP 血浆水平分类为三分位后，我们发现 MMP-3 最低三分位与 IADE 风险较高相关（调整后的优势比 [OR]，2.48；95%置信区间 [CI]，1.17-5.23）。在基因型分析中，5A 等位基因对 IADE 的风险有显著的附加作用，调整后的 OR 为 1.62（95%CI，1.03-2.55）。
在本队列的白种人脑卒中患者中，IADE 与 MMP-3 血浆水平较低和 MMP-3 启动子区域的 5A/6A 多态性相关。这些结果表明 MMP-3 可能在 IADE 中发挥作用。
