RNF213 p.R4810K 与颅外颈动脉病变的独立关联
结果显示该变异携带者ECAD风险升高，且在校正血管危险因素和颅内动脉粥样硬化性疾病（ICAD）后仍显著。关联强度随ECAD狭窄程度递增，闭塞时关联最强。
要点
- RNF213 p.R4810K携带者ECAD风险升高，独立于ICAD。
- 该变异与ECAD严重程度呈分级关联，闭塞时关联最强。
- 颅外病变表达可能涉及不同于ICAD的调控因素。
核心结论
- RNF213 p.R4810K变异与ECAD独立相关，且关联强度随ECAD严重程度递增。
主要发现
- 359例患者（2.6%）携带RNF213 p.R4810K变异，2181例患者（15.6%）存在ECAD，其中78例为变异携带者。
- 校正血管危险因素和ICAD后，变异携带者ECAD风险显著升高，OR为1.69（95%CI 1.29–2.22）。
- 无论是否合并ICAD，该关联保持一致（Pheterogeneity=0.32）。
- ECAD严重程度分析显示关联随狭窄程度递增，闭塞时OR为4.55（95%CI 2.81–7.38）。
关键数值与推荐
- ECAD定义为颅外颈动脉狭窄≥50%或闭塞。
- RNF213 p.R4810K基因型分为非携带者（G/G）和变异携带者（G/A或A/A）。
临床怎么用
- 对于携带RNF213 p.R4810K变异的缺血性卒中或TIA患者，应注意评估颅外颈动脉病变。
以上解读依据论文摘要（全文未开放获取或许可不允许翻译转载）。
原文
Stroke, Volume 57, Issue 10, Page 3046-3054, October 1, 2026. BACKGROUND:TheRNF213p.R4810K variant, a susceptibility variant for moyamoya disease, has also been linked to intracranial atherosclerotic disease (ICAD). However, its association with extracranial carotid artery disease (ECAD), particularly whether this association is independent of concomitant ICAD and whether it differs by stenosis severity, remains unclear.METHODS:We conducted a multicenter registry-based observational study of patients with acute ischemic stroke (AIS) or transient ischemic attack enrolled in the Fukuoka Stroke Registry. Patients were genotyped forRNF213p.R4810K and classified as noncarriers (G/G) or variant carriers (G/A or A/A). ECAD was defined as ≥50% stenosis or occlusion of the extracranial carotid arteries. Multivariable logistic regression was used to assess the association betweenRNF213p.R4810K and ECAD after adjusting for vascular risk factors and ICAD, and stratified analyses were performed by ICAD status. ECAD severity was modeled ordinally (none, moderate, severe, and occlusion) using a partial proportional-odds model.RESULTS:Of 15 569 registry patients with AIS or transient ischemic attack, 13 994 were included in the present analysis after exclusions (mean age, 73±12 years; 59.5% men). TheRNF213p.R4810K variant was identified in 359 patients (2.6%). ECAD was present in 2181 patients (15.6%), including 78 variant carriers. Variant carriers had significantly higher odds of ECAD after adjustment for vascular risk factors and ICAD (odds ratio, 1.69 [95% CI, 1.29–2.22]). This association was consistent irrespective of ICAD status (Pheterogeneity=0.32). In severity analyses, the association strengthened stepwise with increasing ECAD severity; the largest effect estimate was for occlusion (odds ratio, 4.55 [95% CI, 2.81–7.38]).CONCLUSIONS:TheRNF213p.R4810K variant was associated with ECAD independent of concomitant ICAD and showed a graded association with ECAD severity. Extracranial disease expression may involve modifiers distinct from those driving ICAD.
引用
- Stroke：Independent Association of RNF213 p.R4810K With Extracranial Carotid Artery Disease Beyond Intracranial Atherosclerosis
供执业医师工作参考，不替代临床判断；数值与分级以指南原文为准。