Clonal Hematopoiesis Linked to Coronary Heart Disease
CHIP linked to coronary heart disease, myocardial infarction in humans; atherosclerosis in mice
THURSDAY, June 22, 2017 (HealthDay News) -- The presence of clonal hematopoiesis of indeterminate potential (CHIP) is associated with coronary heart disease, according to research published online June 21 in the New England Journal of Medicine.
Siddhartha Jaiswal, M.D., from Massachusetts General Hospital in Boston, and colleagues used whole-exome sequencing to detect the presence of CHIP in peripheral blood cells, and its correlation with coronary heart disease. Samples were obtained from four case-control studies with 4,726 participants with coronary heart disease and 3,529 controls.
The researchers found that carriers of CHIP had a 1.9-fold increased risk of coronary heart disease versus noncarriers in nested case-control analyses from two prospective cohorts. Participants with CHIP had a four-fold increased risk compared with noncarriers in two retrospective case-control cohorts for evaluation of early-onset myocardial infarction. There were associations for mutations in DNMT3A, TET2, ASXL1, and JAK2 with coronary heart disease. Increased coronary artery calcification was seen for CHIP carriers with these mutations. Larger atherosclerotic lesions in the aortic root and aorta were seen in hypercholesterolemia-prone mice that were engrafted with bone marrow obtained from homozygous or heterozygous Tet2 knockout mice. Elevated expression of several chemokine and cytokine genes that contribute to atherosclerosis were seen in analyses of macrophages from Tet2 knockout mice.
"The presence of CHIP in peripheral-blood cells was associated with nearly a doubling in the risk of coronary heart disease in humans and with accelerated atherosclerosis in mice," the authors write.