Liu Xinyuan, Xue Huiwen, Wirdefeldt Karin, Song Huan, Smedby Karin, Fang Fang, Liu Qianwei
Center for Intelligent Medicine Research, Greater Bay Area Institute of Precision Medicine (Guangzhou), State Key Laboratory of Genetic Engineering, Center for Evolutionary Biology, School of Life Sciences, Fudan University, Guangzhou, China.
Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
J Intern Med. 2024 Oct;296(4):327-335. doi: 10.1111/joim.20001. Epub 2024 Jul 29.
BACKGROUND: Little is known regarding the association between clonal hematopoiesis of indeterminate potential (CHIP) and risk of neurodegenerative diseases. OBJECTIVE: To estimate the risk of neurodegenerative diseases among individuals with CHIP. METHODS: We conducted a community-based cohort study based on UK Biobank and used Cox regression to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the risk of any neurodegenerative disease, subtypes of neurodegenerative diseases (including primary neurodegenerative diseases, vascular neurodegenerative diseases, and other neurodegenerative diseases), and specific diagnoses of neurodegenerative diseases (i.e., amyotrophic lateral sclerosis [ALS], Alzheimer's disease [AD], and Parkinson's disease [PD]) associated with CHIP. RESULTS: We identified 14,440 individuals with CHIP and 450,907 individuals without CHIP. Individuals with CHIP had an increased risk of any neurodegenerative disease (HR 1.10, 95% CI: 1.01-1.19). We also observed a statistically significantly increased risk for vascular neurodegenerative diseases (HR 1.31, 95% CI 1.05-1.63) and ALS (HR 1.50, 95% CI 1.05-2.15). An increased risk was also noted for other neurodegenerative diseases (HR 1.13, 95% CI 0.97-1.32), although not statistically significant. Null association was noted for primary neurodegenerative diseases (HR 1.06, 95% CI 0.96-1.17), AD (HR 1.04, 95% CI 0.88-1.23), and PD (HR 1.02, 95% CI 0.86-1.21). The risk increase in any neurodegenerative disease was mainly observed for DNMT3A-mutant CHIP, ASXL1-mutant CHIP, or SRSF2-mutant CHIP. CONCLUSION: Individuals with CHIP were at an increased risk of neurodegenerative diseases, primarily vascular neurodegenerative diseases and ALS, but potentially also other neurodegenerative diseases. These findings suggest potential shared mechanisms between CHIP and neurodegenerative diseases.
背景：关于不确定潜能的克隆性造血（CHIP）与神经退行性疾病风险之间的关联，目前所知甚少。 目的：评估患有CHIP的个体患神经退行性疾病的风险。 方法：我们基于英国生物银行开展了一项社区队列研究，并使用Cox回归来估计患有CHIP的个体患任何神经退行性疾病、神经退行性疾病亚型（包括原发性神经退行性疾病、血管性神经退行性疾病和其他神经退行性疾病）以及特定神经退行性疾病诊断（即肌萎缩侧索硬化症[ALS]、阿尔茨海默病[AD]和帕金森病[PD]）的风险比（HRs）和95%置信区间（CIs）。 结果：我们识别出14440例患有CHIP的个体和450907例未患有CHIP的个体。患有CHIP的个体患任何神经退行性疾病的风险增加（HR 1.10，95%CI：1.01-1.19）。我们还观察到血管性神经退行性疾病（HR 1.31，95%CI 1.05-1.63）和ALS（HR 1.50，95%CI 1.05-2.15）的风险在统计学上显著增加。其他神经退行性疾病的风险也有所增加（HR 1.13，95%CI 0.97-1.32），尽管无统计学意义。原发性神经退行性疾病（HR 1.06，95%CI 0.96-1.17）、AD（HR 1.04，95%CI 0.88-1.23）和PD（HR 1.02，95%CI 0.86-1.21）未发现关联。任何神经退行性疾病的风险增加主要见于DNMT3A突变型CHIP、ASXL1突变型CHIP或SRSF2突变型CHIP。 结论：患有CHIP的个体患神经退行性疾病的风险增加，主要是血管性神经退行性疾病和ALS，但也可能包括其他神经退行性疾病。这些发现提示CHIP与神经退行性疾病之间可能存在共同机制。
Arterioscler Thromb Vasc Biol. 2025-7
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