Lee Eung-Joon, An Hong Yul, Lim Jiwoo, Park Kyung-Il, Choi Su-Yeon, Jeong Han-Yeong, Kang Dong-Wan, Yang Wookjin, Kim Jeong-Min, Ko Sang-Bae, Lee Seung-Hoon, Yoon Byung-Woo, Koh Youngil, Jung Keun-Hwa
Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
Genome Opinion Incorporation, Seoul, South Korea.
Ann Neurol. 2023 Nov;94(5):836-847. doi: 10.1002/ana.26754. Epub 2023 Aug 12.
The effect of clonal hematopoiesis of indeterminate potential (CHIP) on the manifestation and clinical outcomes of acute ischemic stroke (AIS) has not been fully elucidated.
Patients with AIS were included from a prospective registry coupled with a DNA repository. Targeted next-generation sequencing on 25 genes that are frequently mutated in hematologic neoplasms was performed. The prevalence of CHIP was compared between patients with AIS and age-matched healthy individuals. A multivariate linear or logistic regression model was used to assess the association among CHIP and stroke severity, hemorrhagic transformation, and functional outcome at 90 days.
In total, 380 patients with AIS (mean age = 67.2 ± 12.7 years; 41.3% women) and 446 age-matched controls (mean age = 67.2 ± 8.7 years; 31.4% women) were analyzed. The prevalence of CHIP was significantly higher in patients with AIS than in the healthy controls (29.0 vs 22.0%, with variant allele frequencies of 1.5%, p = 0.024). PPM1D was found to be most significantly associated with incident AIS (adjusted odds ratio [aOR] = 7.85, 95% confidence interval [CI] = 1.83-33.63, p = 0.006). The presence of CHIP was significantly associated with the initial National Institutes of Health Stroke Scale (NIHSS) score (β = 1.67, p = 0.022). Furthermore, CHIP was independently associated with the occurrence of hemorrhagic transformation (65/110 clonal hematopoiesis positive [CH+] vs 56/270 CH negative [CH-], aOR = 5.63, 95% CI = 3.24-9.77, p < 0.001) and 90-day functional disability (72/110 [CH+] vs 99/270 [CH-], aOR = 2.15, 95% CI = 1.20-3.88, p = 0.011).
CH was significantly associated with incident AIS. Moreover, particularly, sequence variations in PPM1D, TET2, and DNMT3A represent a new prognostic factor for AIS. ANN NEUROL 2023;94:836-847.
尚不完全清楚不确定潜能的克隆性造血（CHIP）对急性缺血性卒中（AIS）表现及临床结局的影响。
从一个前瞻性登记库及DNA储存库纳入AIS患者。对血液系统肿瘤中频繁突变的25个基因进行靶向二代测序。比较AIS患者与年龄匹配的健康个体中CHIP的患病率。采用多变量线性或逻辑回归模型评估CHIP与卒中严重程度、出血转化及90天时功能结局之间的关联。
共分析了380例AIS患者（平均年龄=67.2±12.7岁；41.3%为女性）和446例年龄匹配的对照者（平均年龄=67.2±8.7岁；31.4%为女性）。AIS患者中CHIP的患病率显著高于健康对照者（29.0%对22.0%，变异等位基因频率为1.5%，p=0.024）。发现PPM1D与AIS发病最显著相关（校正比值比[aOR]=7.85，95%置信区间[CI]=1.83 - 33.63，p=0.006）。CHIP的存在与初始美国国立卫生研究院卒中量表（NIHSS）评分显著相关（β=1.67，p=0.022）。此外，CHIP与出血转化的发生独立相关（110例克隆性造血阳性[CH+]中有65例，270例CH阴性[CH-]中有56例，aOR=5.63，95% CI=3.24 - 9.77，p<0.001）以及90天时的功能残疾（110例[CH+]中有72例，270例[CH-]中有99例，aOR=2.15，95% CI=1.20 - 3.88，p=0.011）。
CH与AIS发病显著相关。此外，特别地，PPM1D、TET2和DNMT3A中的序列变异代表了AIS的一个新的预后因素。《神经病学纪事》2023年；94:836 - 847。
