Department of Neurology School of Medicine Samsung Medical CenterSungkyunkwan University Seoul South Korea.
J Am Heart Assoc. 2021 Jan 5;10(1):e017660. doi: 10.1161/JAHA.120.017660. Epub 2020 Dec 25.
Background The ( gene) variant R4810K is a susceptibility allele not only for Moyamoya disease (MMD) but also for intracranial atherosclerosis (ICAS) in East Asian populations. We hypothesized that this variant would affect the distribution of ICAS and recurrence of cerebrovascular events. Methods and Results We conducted a prospective study of patients with ICAS and MMD using high-resolution magnetic resonance imaging and R4810K genotyping. Patients were included in the ICAS group when relevant plaques existed on high-resolution magnetic resonance imagingand in the MMD group when they carried the variant and high-resolution magnetic resonance imaging showed no plaques but characteristic features of MMD. We compared clinical and neuroimaging features of patients with ICAS-+ with patients with ICAS-- and of patients with MMD. Of 477 patients, 238 patients were in the ICAS group and 239 were in the MMD group. Among patients with ICAS, 79 patients (33.2%) were in the ICAS-+ group and 159 (66.8%) in the ICAS-- group. Tandem lesions were significantly more common in the ICAS- group than in the ICAS-- group (40.3% versus 72.2%, <0.001), and their distributions were similar between the ICAS- and MMD groups. The presence of the R4810K variant (hazard ratio [HR], 3.203; 95% CI, 1.149-9.459; =0.026) and tandem lesions (≥3) (HR, 8.315; 95% CI, 1.930-39.607; =0.005) were independently associated with recurrent cerebrovascular events. Conclusions Patients with ICAS carrying the R4810K variant showed clinical and imaging features distinct from patients with ICAS without the variant, suggesting that the R4810K variant plays a role in intracranial atherosclerosis in East Asian patients.
（基因）变体 R4810K 不仅是东亚人群中 Moyamoya 病（MMD）的易感等位基因，也是颅内动脉粥样硬化（ICAS）的易感等位基因。我们假设该变体将影响 ICAS 的分布和脑血管事件的复发。
我们使用高分辨率磁共振成像和 R4810K 基因分型对 ICAS 和 MMD 患者进行了前瞻性研究。当高分辨率磁共振成像上存在相关斑块时，患者被纳入 ICAS 组，当他们携带变体且高分辨率磁共振成像上无斑块但存在 MMD 的特征时，患者被纳入 MMD 组。我们比较了 ICAS-+患者与 ICAS--患者和 MMD 患者的临床和神经影像学特征。在 477 名患者中，238 名患者在 ICAS 组，239 名患者在 MMD 组。在 ICAS 患者中，79 名（33.2%）患者在 ICAS-+组，159 名（66.8%）患者在 ICAS--组。串联病变在 ICAS-+组中明显比在 ICAS--组中更常见（40.3%比 72.2%，<0.001），并且它们在 ICAS-和 MMD 组之间的分布相似。R4810K 变体的存在（危险比[HR]，3.203；95%置信区间，1.149-9.459；=0.026）和串联病变（≥3）（HR，8.315；95%置信区间，1.930-39.607；=0.005）与复发性脑血管事件独立相关。
携带 R4810K 变体的 ICAS 患者表现出与不携带变体的 ICAS 患者不同的临床和影像学特征，表明 R4810K 变体在东亚患者的颅内动脉粥样硬化中起作用。
