Parkinson's disease is associated with clonal hematopoiesis with TET2 mutation

被引:0
作者
Woo, Kyung Ah [1 ]
Kim, Han-Joon [1 ]
Lee, Chan Young [2 ]
Shin, Jung Hwan [1 ]
Sun, Choonghyun [3 ]
Im, Hogune [3 ]
An, Hongyul [3 ]
Lim, Jiwoo [3 ]
Choi, Su-Yeon [4 ]
Koh, Youngil [3 ,5 ]
Jeon, Beomseok [1 ]
机构
[1] Seoul Natl Univ, Coll Med, Dept Neurol, Seoul Natl Univ Hosp, Seoul, South Korea
[2] Ewha Womans Univ, Coll Med, Dept Neurol, Mokdong Hosp, Seoul, South Korea
[3] NOBO Med Inc, Seoul, South Korea
[4] Seoul Natl Univ, Coll Med, Seoul Natl Univ Hosp Healthcare Syst, Dept Internal Med,Gangnam Ctr, Seoul, South Korea
[5] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul Natl Univ Hosp, Seoul, South Korea
基金
新加坡国家研究基金会;
关键词
TNF-ALPHA; NEURODEGENERATION; INFLAMMATION; ACTIVATION; MARKERS; RISK;
D O I
10.1038/s41531-024-00784-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
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页数:7
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