Clonal hematopoiesis with DNMT3A mutations is associated with multiple system atrophy

Abstract

Background: Clonal hematopoiesis of indeterminate potential (CHIP) is associated with cardiovascular diseases and other disorders, possibly via inflammation. Recent research suggests a connection of CHIP with neurodegenerative disorders.

Objective: We aimed to investigate the association between multiple system atrophy (MSA) and CHIP.

Methods: We included 100 patients with MSA and 4457 controls. Targeted sequencing of peripheral blood DNA samples was performed, focusing on a panel of 25 genes commonly.

Linked to chip: The prevalence of CHIP in patients with MSA was assessed against controls at variant allele frequency (VAF) thresholds of 1.5 % and 2.0 %.

Results: DNMT3A mutation rates were significantly higher in patients with MSA, with a VAF of 1.5 %, which remained significant after adjusting for age and sex (adjusted odds ratio, 1.848; 95 % CI, 1.024-3.335; p = 0.0416).

Conclusion: Our results suggest an association between DNMT3A mutations and MSA.

Keywords: Clonal hematopoiesis; DNMT3A; Multiple system atrophy.