Plaque erosion risk and JAK2 V617F variant

BACKGROUND AND AIMS: Clonal haematopoiesis of indeterminate potential (CHIP) can increase the risk of myocardial infarction (MI). Among various CHIP mutations, JAK2 V617F substantially elevated this risk. However, the specific associations between JAK2 V617F and two mechanisms of MI, plaque erosion and plaque rupture, remain unclear. METHODS: Case-control studies investigated these associations. A total of 728 erosion cases, 919 rupture cases, and 804 controls were included from our centre. Digital-drop polymerase chain reaction was performed on these individuals to identify the presence of JAK2 V617F. Previous experimental work has implicated neutrophils in the pathogenesis of erosion in the presence of this mutation. Thus, single-cell RNA sequencing of neutrophils from both JAK2 V617F carriers and healthy donors was performed to seek the potential mechanisms responsible for erosion associated with JAK2 V617F. RESULTS: Among the participants, 26 (3.57%) erosion patients, 7 (.76%) rupture patients, and 3 (.37%) controls were identified as JAK2 V617F carriers with a variant allele frequency (VAF) ≥1%. The carriers among the erosion patients exhibited higher platelet counts and lower glycated haemoglobin and blood lipid levels. Logistic regression analysis, considering erosion or rupture as separate cases, revealed that JAK2 V617F carriers with a VAF ≥1% showed a significant association with erosion [odds ratio (OR) 16.246, 95% confidence interval (CI) 4.624-57.080, P < .0001], but not with rupture (OR 1.677, 95% CI .379-7.415, P = .495). Single-cell RNA-sequencing data indicated that neutrophils from JAK2 V617F carriers displayed augmented expression levels of genes and gene sets associated with activation, adhesion, migration, and granule secretion. CONCLUSIONS: JAK2 V617F linked to a high risk of erosion, an association to which enhanced neutrophil activation may contribute.