Shimada Daisuke, Miyawaki Satoru, Nakanishi Kaoru, Jono Takashi, Maruoka Hibiku, Kawai Takuya, Harada Yoichi, Kono Takuji, Komatsubara Koichiro, Nakauchi Jun, Matsumoto Yoshie, Okada Kei, Dofuku Shogo, Hongo Hiroki, Mitsui Jun, Teranishi Yu, Ohara Kenta, Ishigami Daiichiro, Sakai Yu, Kawano Hiroyuki, Noguchi Akio, Nakatomi Hirofumi, Saito Nobuhito, Hirano Teruyuki, Shiokawa Yoshiaki
Department of Neurosurgery, Kyorin University Faculty of Medicine, Tokyo 181-8611, Japan.
Department of Neurosurgery, Faculty of Medicine, The University of Tokyo, Tokyo 113-8654, Japan.
Brain Commun. 2025 Jan 31;7(1):fcaf049. doi: 10.1093/braincomms/fcaf049. eCollection 2025.
() p.Arg4810Lys (c.14429G > A) is associated with intracranial artery stenosis; however, its association with extracranial artery stenosis remains unknown. We aimed to elucidate the clinical significance and association of p.Arg4810Lys with stroke subtypes, extracranial artery stenosis, and maximum intima-media thickness. A cohort of 600 patients with stroke prospectively collected over 1 year was assessed for the presence of p.Arg4810Lys. A total of 1202 patients served as controls. The association of p.Arg4810Lys with various stroke subtypes was studied. In sub-analyses, the association of p.Arg4810Lys with intracranial artery stenosis/extracranial artery stenosis and maximum intima-media thickness were assessed. p.Arg4810Lys was more common in patients with stroke (3.3%) than in those without stroke (1.1%). p.Arg4810Lys was significantly associated with stroke. Among various stroke subtypes, large-artery atherosclerosis, both due to intracranial artery stenosis and extracranial artery stenosis, was most significantly associated with p.Arg4810Lys. In the sub-analysis, intracranial artery stenosis-only, extracranial artery stenosis-only, and concurrent intracranial artery stenosis and extracranial artery stenosis groups were significantly associated with p.Arg4810Lys, regardless of stroke type (adjusted odds ratio, 3.72; 95% confidence interval, 1.30-10.60; 0.014, adjusted odds ratio, 7.04; 95% confidence interval, 1.51-32.77; 0.013, adjusted odds ratio, 11.68; 95% confidence interval, 4.25-32.07; 0.001, respectively). p.Arg4810Lys was associated with increased maximum intima-media thickness, measured using carotid artery ultrasonography (multiple regression analysis β = 0.165; = 0.004). These results were replicated in an independent validation cohort. In conclusion, p.Arg4810Lys increases the risk of stroke. In addition to intracranial artery stenosis, p.Arg4810Lys is associated with extracranial artery stenosis and maximum intima-media thickness. Evaluating p.Arg4810Lys may help predict the incidence and type of stroke.
p.Arg4810Lys（c.14429G＞A）与颅内动脉狭窄相关；然而，其与颅外动脉狭窄的关联尚不清楚。我们旨在阐明p.Arg4810Lys与卒中亚型、颅外动脉狭窄及最大内膜中层厚度的临床意义和关联。对前瞻性收集的1年内600例卒中患者队列进行p.Arg4810Lys检测。共1202例患者作为对照。研究了p.Arg4810Lys与各种卒中亚型的关联。在亚分析中，评估了p.Arg4810Lys与颅内动脉狭窄/颅外动脉狭窄及最大内膜中层厚度的关联。p.Arg4810Lys在卒中患者中（3.3%）比无卒中患者（1.1%）更常见。p.Arg4810Lys与卒中显著相关。在各种卒中亚型中，因颅内动脉狭窄和颅外动脉狭窄导致的大动脉粥样硬化与p.Arg4810Lys的关联最为显著。在亚分析中，仅颅内动脉狭窄组、仅颅外动脉狭窄组以及颅内动脉狭窄合并颅外动脉狭窄组均与p.Arg4810Lys显著相关，无论卒中类型如何（校正比值比分别为3.72；95%置信区间为1.30 - 10.60；P = 0.014，校正比值比为7.04；95%置信区间为1.51 - 32.77；P = 0.013，校正比值比为11.68；95%置信区间为4.25 - 32.07；P = 0.001）。p.Arg4810Lys与使用颈动脉超声测量的最大内膜中层厚度增加相关（多元回归分析β = 0.165；P = 0.004）。这些结果在独立验证队列中得到重复。总之，p.Arg4810Lys增加卒中风险。除颅内动脉狭窄外，p.Arg4810Lys还与颅外动脉狭窄及最大内膜中层厚度相关。评估p.Arg4810Lys可能有助于预测卒中的发生率和类型。
