TP53-mediated clonal hematopoiesis confers increased risk for incident atherosclerotic disease

Somatic and Germline Variants and Coronary Heart Disease in a Chinese Population

“…Second, we provided substantial evidence that supported the impact of the 2 most frequently mutated genes, DNMT3A and TET2 , on CHD development in East Asian individuals. Of note, the association of DNMT3A -CHIP with CHD remains controversial in previous studies, although TET2 has demonstrated consistent associations . It is plausible that this disparity in the findings of DNMT3A could arise from differences in sequencing depth.…”

Clonal hematopoiesis: the nonhereditary genetics of age-associated cardiovascular disease

“…Experimental studies have provided evidence for a mechanistic link between hematopoietic mutations in CHIP driver genes and CVD. Although most studies have focused on models of TET2 CH, other CHIP genes examined include DNMT3A, ASXL1, JAK2, TP53, and PPM1D, and the experimental models have included atherosclerosis, ischemic and nonischemic heart failure, doxorubicin-induced cardiac toxicity, and others [8,[27][28][29][30][31][32][33]. Although functional differences have been observed between the different CHIP driver genes, all appear to promote inflammatory processes.…”

Clonal hematopoiesis of indeterminate potential and clonal cytopenias of undetermined significance: 2023 update on clinical associations and management recommendations

“…Vascular events were independently associated with CH, even when adjusted for variables such as advanced age, high body mass index, type 2 diabetes mellitus, gender, and hypertension, and recent studies have shown accelerated vascular plaque formation in TET2 knockout mice models, 7,8 suggesting a causal link between CH and atherosclerotic vascular disease. Similarly, when atherosclerosis‐prone Ldlr −/− mice were transplanted with p53‐deficient hematopoietic cells, they were found to have increased aortic atherosclerotic plaque size and macrophage accumulation 9 . Several papers have highlighted novel associations with other non‐malignant human conditions such as type 2 diabetes mellitus, 6,10 osteoporosis, 11 chronic obstructive pulmonary disease, 12 gout, 13 and venous thrombosis, 14 and severity of chronic ischemic heart failure 15 .…”

“…Similarly, when atherosclerosis-prone Ldlr À/À mice were transplanted with p53-deficient hematopoietic cells, they were found to have increased aortic atherosclerotic plaque size and macrophage accumulation. 9 Several papers have highlighted novel associations with other nonmalignant human conditions such as type 2 diabetes mellitus, 6,10 osteoporosis, 11 chronic obstructive pulmonary disease, 12 gout, 13 and venous thrombosis, 14 and severity of chronic ischemic heart failure. 15 However, the clinical applications of CH testing are still limited due to lack of prospective data, especially over the uncertainty that does an early diagnosis of CH offers any measurable clinical benefit.…”