Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke
Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular di...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-12-01
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| Series: | European Journal of Medical Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40001-023-01566-w |
| _version_ | 1797388513372536832 |
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| author | Xin Qiu Jiaxu Weng Yingyu Jiang Lingyun Cui Hongqiu Gu Yong Jiang Yalun Dai Hao Li Yongjun Wang Zixiao Li |
| author_facet | Xin Qiu Jiaxu Weng Yingyu Jiang Lingyun Cui Hongqiu Gu Yong Jiang Yalun Dai Hao Li Yongjun Wang Zixiao Li |
| author_sort | Xin Qiu |
| collection | DOAJ |
| description | Abstract Background Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular disease through the activation of the interleukin 6 (IL-6) pathway; however, its role on unfavorable functional outcomes in different etiologies of ischemic stroke remains unclear. We aimed to investigate the association between CHIP-related gene mutations and unfavorable functional outcomes of ischemic stroke with different etiologies. Methods We prospectively studied a cohort of 3396 stroke patients with identified etiologies, and identified CHIP and the presence of the IL6R variant (IL6R p.Asp358Ala) by whole-genome sequencing. The IL6R p.Asp358Ala coding mutation was used as a genetic inhibition for IL-6 signaling. The primary outcome was unfavorable functional outcome [(Modified Rankin Scale), mRS 2–6] at 3 months. Results Of the 3396 patients, 110 (3.2%) were CHIP carriers and the median age was 62 years (IQR, 54.0–69.0). The CHIP increased the risk of unfavorable functional outcome among patients with hyper-inflammation status of high-sensitivity C-reactive protein (hsCRP) > median levels in patients with large-artery atherosclerosis (LAA) (OR 2.45, 95% CI 1.00–5.98, p = 0.049, p interaction = 0.01). Presence of IL6R variant (IL6R p.Asp358Ala) could attenuate the risk of unfavorable functional outcome only in patients with CHIP (OR 0.30, 95%CI 0.12–0.76, p = 0.01, p interaction = 0.02), and especially in LAA patients with CHIP (OR 0.1, 95%CI 0.02–0.42, p = 0.002; p interaction = 0.001). Conclusion CHIP is associated with unfavorable functional outcomes in patients with LAA stroke and hyper-inflammation. Genetic IL-6 signaling inhibition might attenuate the risk of unfavorable functional outcomes in CHIP carriers, especially in LAA stroke patients. |
| first_indexed | 2024-03-08T22:40:56Z |
| format | Article |
| id | doaj.art-f77b81a4b6264b85b5f6bef785789039 |
| institution | Directory Open Access Journal |
| issn | 2047-783X |
| language | English |
| last_indexed | 2024-03-08T22:40:56Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj.art-f77b81a4b6264b85b5f6bef7857890392023-12-17T12:10:54ZengBMCEuropean Journal of Medical Research2047-783X2023-12-012811810.1186/s40001-023-01566-wAssociation between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic strokeXin Qiu0Jiaxu Weng1Yingyu Jiang2Lingyun Cui3Hongqiu Gu4Yong Jiang5Yalun Dai6Hao Li7Yongjun Wang8Zixiao Li9Department of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityChina National Clinical Research Center for Neurological DiseasesDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityChina National Clinical Research Center for Neurological DiseasesChina National Clinical Research Center for Neurological DiseasesChina National Clinical Research Center for Neurological DiseasesDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityDepartment of Neurology, Beijing Tiantan Hospital, Capital Medical UniversityAbstract Background Clonal hematopoiesis of indeterminate potential (CHIP) is a phenomenon that characterizes individuals with somatic mutations that are related to hematologic malignancy but without hematologic abnormalities. Presence of CHIP is associated with the atherosclerotic cardiovascular disease through the activation of the interleukin 6 (IL-6) pathway; however, its role on unfavorable functional outcomes in different etiologies of ischemic stroke remains unclear. We aimed to investigate the association between CHIP-related gene mutations and unfavorable functional outcomes of ischemic stroke with different etiologies. Methods We prospectively studied a cohort of 3396 stroke patients with identified etiologies, and identified CHIP and the presence of the IL6R variant (IL6R p.Asp358Ala) by whole-genome sequencing. The IL6R p.Asp358Ala coding mutation was used as a genetic inhibition for IL-6 signaling. The primary outcome was unfavorable functional outcome [(Modified Rankin Scale), mRS 2–6] at 3 months. Results Of the 3396 patients, 110 (3.2%) were CHIP carriers and the median age was 62 years (IQR, 54.0–69.0). The CHIP increased the risk of unfavorable functional outcome among patients with hyper-inflammation status of high-sensitivity C-reactive protein (hsCRP) > median levels in patients with large-artery atherosclerosis (LAA) (OR 2.45, 95% CI 1.00–5.98, p = 0.049, p interaction = 0.01). Presence of IL6R variant (IL6R p.Asp358Ala) could attenuate the risk of unfavorable functional outcome only in patients with CHIP (OR 0.30, 95%CI 0.12–0.76, p = 0.01, p interaction = 0.02), and especially in LAA patients with CHIP (OR 0.1, 95%CI 0.02–0.42, p = 0.002; p interaction = 0.001). Conclusion CHIP is associated with unfavorable functional outcomes in patients with LAA stroke and hyper-inflammation. Genetic IL-6 signaling inhibition might attenuate the risk of unfavorable functional outcomes in CHIP carriers, especially in LAA stroke patients.https://doi.org/10.1186/s40001-023-01566-wClonal hematopoiesisStrokeFunctional outcomeInterleukin-6 |
| spellingShingle | Xin Qiu Jiaxu Weng Yingyu Jiang Lingyun Cui Hongqiu Gu Yong Jiang Yalun Dai Hao Li Yongjun Wang Zixiao Li Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke European Journal of Medical Research Clonal hematopoiesis Stroke Functional outcome Interleukin-6 |
| title | Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke |
| title_full | Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke |
| title_fullStr | Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke |
| title_full_unstemmed | Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke |
| title_short | Association between clonal hematopoiesis-related gene mutations and unfavorable functional outcome in patients with large-artery atherosclerotic stroke |
| title_sort | association between clonal hematopoiesis related gene mutations and unfavorable functional outcome in patients with large artery atherosclerotic stroke |
| topic | Clonal hematopoiesis Stroke Functional outcome Interleukin-6 |
| url | https://doi.org/10.1186/s40001-023-01566-w |
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