Department of Neurology, Seoul National University Bundang Hospital, Seongnam-si, South Korea.
Department of Neurology, Seoul National University Hospital, Seoul, South Korea.
CNS Neurosci Ther. 2023 May;29(5):1243-1253. doi: 10.1111/cns.14114. Epub 2023 Feb 21.
Clonal hematopoiesis of indeterminate potential (CHIP) increases the risk of cerebrovascular events, while its association with cerebral white matter hyperintensity (WMH) is undemonstrated. We evaluated the effect of CHIP and its major driving mutations on cerebral WMH severity.
From an institutional cohort of a routine health check-up program with a DNA repository database, subjects who were ≥50 years of age, with one or more cardiovascular risk factors but no central nervous system disorder, and performed brain MRI were included. Along with the presence of CHIP and its major driving mutations, clinical and laboratory data were obtained. WMH volume was measured in total, periventricular, and subcortical regions.
Among the total 964 subjects, 160 subjects were classified as CHIP positive group. CHIP was most frequently associated with DNMT3A mutation (48.8%), followed by TET2 (11.9%) and ASXL1 (8.1%) mutations. Linear regression analysis adjusting for age, sex, and conventional cerebrovascular risk factors suggested that CHIP with DNMT3A mutation was associated with the lower log-transformed total WMH volume, unlike other CHIP mutations. When classified according to variant allele fraction (VAF) value of DNMT3A mutation, higher VAF classes were associated with the lower log-transformed total WMH and the lower log-transformed periventricular WMH volume, but not with the log-transformed subcortical WMH volumes.
Clonal hematopoiesis with DNMT3A mutation is quantitatively associated with a lower volume of cerebral WMH, especially in the periventricular region. CHIP with DNMT3A mutation might have a protective role in the endothelial pathomechanism of WMH.
不确定潜能的克隆性造血（CHIP）增加了脑血管事件的风险，但其与脑白质高信号（WMH）的关系尚未得到证实。我们评估了 CHIP 及其主要驱动突变对脑 WMH 严重程度的影响。
从一个常规健康检查计划的机构队列中，我们选择了年龄≥50 岁、有一个或多个心血管危险因素但无中枢神经系统疾病且进行了脑部 MRI 的患者。我们获得了 CHIP 及其主要驱动突变的存在情况以及临床和实验室数据。测量了总脑白质、脑室周围和皮质下区域的 WMH 体积。
在总共 964 名受试者中，有 160 名被归类为 CHIP 阳性组。CHIP 最常与 DNMT3A 突变相关（48.8%），其次是 TET2（11.9%）和 ASXL1（8.1%）突变。线性回归分析调整了年龄、性别和传统的脑血管危险因素，表明与其他 CHIP 突变不同，携带 DNMT3A 突变的 CHIP 与较低的总 WMH 对数转换体积相关。当根据 DNMT3A 突变的变异等位基因分数（VAF）值进行分类时，较高的 VAF 类与较低的总 WMH 和较低的脑室周围 WMH 对数转换体积相关，但与皮质下 WMH 体积的对数转换无关。
携带 DNMT3A 突变的克隆性造血与脑 WMH 体积较低呈定量相关，特别是在脑室周围区域。携带 DNMT3A 突变的 CHIP 可能在 WMH 的血管内皮病理机制中具有保护作用。
