AI Article Synopsis

  • Clonal hematopoiesis of indeterminate potential (CHIP) involves mutations in myeloid cancer-related genes, and recent research suggests it may have a genetic basis.
  • A study of 594 elderly twins found that about 36% had relevant mutations, yet there was no significant genetic predisposition identified between monozygotic and dizygotic twins.
  • Additionally, the study did not confirm that CHIP mutations negatively impacted survival when comparing twins who were discordant for these mutations.

Article Abstract

Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is defined by mutations in myeloid cancer-associated genes with a variant allele frequency of at least 2%. Recent studies have suggested a possible genetic predisposition to CH. To further explore this phenomenon, we conducted a population-based study of 594 twins from 299 pairs aged 73 to 94 years, all with >20 years' follow-up. We sequenced DNA from peripheral blood with a customized 21-gene panel at a median coverage of 6179X. The casewise concordance rates for mutations were calculated to assess genetic predisposition. Mutations were identified in 214 (36%) of the twins. Whereas 20 twin pairs had mutations within the same genes, the exact same mutation was only observed in 2 twin pairs. No significant difference in casewise concordance between monozygotic and dizygotic twins was found for any specific gene, subgroup, or CHIP mutations overall, and no significant heritability could be detected. In pairs discordant for CHIP mutations, we tested if the affected twin died before the unaffected twin, as a direct measurement of the association of having CH when controlling for familial factors. A total of 127 twin pairs were discordant for carrying a mutation, and in 61 (48%) cases, the affected twin died first (P = .72). Overall, we did not find a genetic predisposition to CHIP mutations in this twin study. The previously described negative association of CHIP mutations on survival could not be confirmed in a direct comparison among twin pairs that were discordant for CHIP mutations.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6978157PMC
http://dx.doi.org/10.1182/blood.2019001793DOI Listing

Publication Analysis

Top Keywords

chip mutations
20
twin pairs
16
genetic predisposition
12
pairs discordant
12
mutations
9
clonal hematopoiesis
8
casewise concordance
8
twin
8
discordant chip
8
twin died
8

Similar Publications

CHIP-ing Away at Post-Transplant Outcomes: the Role of Somatic Mutations in Heart Transplant Outcomes.

J Card Fail

December 2024

Division of Cardiology, Duke University School of Medicine, Durham, NC; Duke Molecular Physiology Institute, Duke University School of Medicine, Durham, North Carolina; Duke Center for Precision Health, Duke University School of Medicine, Durham NC. Electronic address:

View Article and Find Full Text PDF

Introduction: The efficacy of radiotherapy in colorectal cancer (CRC) is often limited by radiation resistance. Ataxia telangiectasia mutated (ATM) is well known for its role in repairing double-strand DNA breaks within the DNA damage response (DDR) pathway. However, whether ATM mediates other mechanisms contributing to radiation resistance remains insufficiently investigated.

View Article and Find Full Text PDF

Background: Spinocerebellar ataxias (SCAs) encompass a wide spectrum of inherited neurodegenerative diseases, primarily characterized by pathological changes in the cerebellum, spinal cord, and brainstem degeneration. Autosomal dominant spinocerebellar ataxia type 48 (SCA48) is a newly identified subtype of SCA, marked by early-onset ataxia and cognitive impairment, and is associated with mutations in the STIP1 homology and U-box-containing protein 1 (STUB1) gene. The STUB1 gene encodes the protein CHIP (C-terminus of HSC70-interacting protein) which functions as E3 ubiquitin ligase and is crucial to the development of neural systems.

View Article and Find Full Text PDF

Background: Recently, the incidence of pancreatic cancer (PC) has gradually increased. Research has shown that UTX mutants are critical in tumors. However, the underlying mechanisms remain incompletely understood.

View Article and Find Full Text PDF

BCL2/adenovirus E1B 19-kDa protein-interacting protein 2 homolog (BNIP-H or Caytaxin), a pivotal adaptor protein that facilitates cerebellar cortex growth and synaptic transmission, is posttranslationally modified to regulate neuronal function. This study reports the ubiquitination of BNIP-H by Carboxyl terminus of Hsc70-Interacting Protein (CHIP), a U-box containing E3 ligase that is also regulated autoubiquitination. Specifically, it was observed that CHIP autoubiquitinated itself primarily at Lys23 and Lys31 .

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!

A PHP Error was encountered

Severity: Notice

Message: fwrite(): Write of 34 bytes failed with errno=28 No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 272

Backtrace:

A PHP Error was encountered

Severity: Warning

Message: session_write_close(): Failed to write session data using user defined save handler. (session.save_path: /var/lib/php/sessions)

Filename: Unknown

Line Number: 0

Backtrace: