한빛사논문
- 조회593
Eung-Joon Lee 1, Hong Yul An 2, Jiwoo Lim 2, Kyung-Il Park 1,3, Su-Yeon Choi 4, Han-Yeong Jeong 1, Dong-Wan Kang 1, Wookjin Yang 1, Jeong-Min Kim 1, Sang-Bae Ko 1, Seung-Hoon Lee 1, Byung-Woo Yoon 5, Youngil Koh 2,6, Keun-Hwa Jung 1
1Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, South Korea.
2Genome Opinion Incorporation, Seoul, South Korea.
3Department of Neurology, Seoul National University Healthcare System Gangnam Center, Seoul, South Korea.
4Division of Cardiology, Department of Internal Medicine, Seoul National University Healthcare System Gangnam Center, Seoul, South Korea.
5Department of Neurology, Uijeongbu Eulji Medical Center, Uijeongbu-si, South Korea.
6Division of Hematology and Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea.
CORRESPONDING AUTHOR : Keun-Hwa Jung MD, PhD
Abstract
Objective: 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.
Methods: 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.
Results: 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).
Interpretation: 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.
논문정보
- Research article
- 2023년 08월 (BRIC 등록일 2023-08-17)
- 국내 연구진
- 의약학 > 신경의학
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