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Clonal hematopoiesis in cardiovascular aging: Insights from the verona heart study

Katarzyna Malgorzata Kwiatkowska1, Nicola Martinelli2, Luca Bertamini3,2,4

  • 1Department of Medical and Surgical Sciences (DIMEC), University of Bologna, 40126, Bologna, Italy. katarzyn.kwiatkowsk2@unibo.it.

Geroscience
|October 26, 2024
PubMed

Insights

Clonal hematopoiesis of indeterminate potential (CHIP) is linked to increased cardiovascular disease risk. Our study found higher somatic variant burdens in CAD patients, suggesting CHIP

Area of Science:

  • Hematology
  • Cardiovascular Disease
  • Genetics

Background:

  • Clonal hematopoiesis of indeterminate potential (CHIP) involves somatic mutations in hematopoietic stem cells.
  • CHIP is associated with increased all-cause mortality, primarily from cardiovascular events.
  • Understanding CHIP's role in cardiovascular aging is vital for improving health and lifespan.

Purpose of the Study:

  • To investigate the association between clonal hematopoiesis and cardiovascular aging in the Verona Heart Study (VHS) cohort.
  • To compare somatic variant burdens in individuals with coronary artery disease (CAD) versus healthy controls.
  • To identify specific genes and genetic regions associated with CHIP in the context of CAD.

Main Methods:

  • Deep sequencing and amplicon-based approaches were used to analyze 11 key genes (ASXL1, DNMT3A, IDH1, IDH2, JAK2, PPM1D, SF3B1, SRSF2, TET2, TP53, U2AF1).
  • Samples from 44 CAD patients and 42 age- and sex-matched healthy controls (CAD-FREE) from the VHS cohort were analyzed.
  • Variant burden, including total and disruptive somatic variants, was quantified and compared between groups.

Main Results:

  • Subjects with CAD exhibited a significantly higher total somatic variant burden compared to the CAD-FREE group.
  • Elevated variant rates in specific regions of ASXL1, DNMT3A, IDH2, JAK2, TET2, and U2AF1 were observed in CAD subjects.
  • ASXL1, DNMT3A, IDH2, JAK2, SF3B1, TET2, and TP53 showed substantially higher levels of disruptive variants in the CAD group.

Conclusions:

  • A correlation exists between clonal hematopoiesis and the accumulation of disruptive variants in specific genomic regions within the VHS cohort.
  • These findings suggest a potential role for CHIP and associated genetic variants in the pathophysiology of cardiovascular aging.
  • Further research into CHIP may provide insights into novel therapeutic targets for cardiovascular disease.

Keywords:
AgingClonal hematopoiesisCoronary artery diseaseSomatic mutations

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