Woo Kyung Ah, Kim Han-Joon, Lee Chan Young, Shin Jung Hwan, Sun Choonghyun, Im Hogune, An Hongyul, Lim Jiwoo, Choi Su-Yeon, Koh Youngil, Jeon Beomseok
Department of Neurology, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Republic of Korea.
Department of Neurology, Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Seoul, Republic of Korea.
NPJ Parkinsons Dis. 2024 Sep 6;10(1):168. doi: 10.1038/s41531-024-00784-1.
Clonal hematopoiesis of indeterminate potential (CHIP), a premalignant expansion of mutated hematopoietic stem cells, is linked to immune alterations. Given the role of neuroinflammation and immune dysfunction in Parkinson's disease (PD), we hypothesized a connection between CHIP and PD. We analyzed peripheral blood DNA from 341 PD, 92 isolated REM sleep behavior disorder (iRBD) patients, and 5003 controls using targeted sequencing of 24 genes associated with hematologic neoplasms. PD cases were classified by clinical progression mode: fast, slow, and typical. Using multivariable logistic regression models, CHIP prevalence was assessed against controls with a 1.0% variant allele fraction threshold. CHIP with TET2 mutations was more prevalent in PD than controls (aOR 1.75, 95% CI 1.11-2.77, p = 0.017), particularly in the fast motor progression subgroup (aOR 3.19, p = 0.004). No distinct associations were observed with iRBD. PD is linked to increased odds of CHIP with TET2 mutations, suggesting immune dysregulation in PD pathophysiology.
不确定潜能的克隆性造血（CHIP）是一种突变造血干细胞的癌前扩增，与免疫改变有关。鉴于神经炎症和免疫功能障碍在帕金森病（PD）中的作用，我们推测CHIP与PD之间存在联系。我们使用与血液系统肿瘤相关的24个基因的靶向测序，分析了341例PD患者、92例孤立性快速眼动睡眠行为障碍（iRBD）患者和5003名对照的外周血DNA。PD病例按临床进展模式分类：快速、缓慢和典型。使用多变量逻辑回归模型，以1.0%的变异等位基因分数阈值评估CHIP患病率与对照的情况。与对照相比，携带TET2突变的CHIP在PD中更为普遍（调整后比值比1.75，95%置信区间1.11-2.77，p = 0.017），特别是在快速运动进展亚组中（调整后比值比3.19，p = 0.004）。未观察到与iRBD有明显关联。PD与携带TET2突变的CHIP几率增加有关，提示在PD病理生理学中存在免疫失调。
