| Title: | Clonal Hematopoiesis of Indeterminate Potential Is Associated With Incident Abdominal Aortic Aneurysm |
| Journal: | Arteriosclerosis Thrombosis and Vascular Biology |
| Published: | 8 May 2025 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/40336477/ |
| DOI: | https://doi.org/10.1161/atvbaha.124.322630 |
Publication 15401
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Abstract
BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) is an emerging risk factor for cardiovascular diseases. Genetic IL (interleukin)-6 signaling deficiency reduced cardiovascular disease risk in CHIP carriers. However, the association between CHIP and incident abdominal aortic aneurysm (AAA) and whether IL-6 signaling inhibition attenuates AAA risk among individuals with CHIP remained unclear.</p>
METHODS: Participants without prevalent AAA from the UK Biobank were included. The associations of any CHIP (variant allele fraction, ≥2%), large CHIP (variant allele fraction, ≥10%), and gene-specific CHIP subtypes with incident AAA were investigated. The protection role of IL6R p.Asp358Ala, a genetic proxy for IL-6 deficiency, was tested after stratification by CHIP status. Furthermore, the interaction and joint effects of CHIP and genetic susceptibility on AAA risk were tested.</p>
RESULTS: This study included 425 211 participants. Any CHIP and large CHIP was identified in 13 768 (3.2%) and 8576 (2.0%) participants, respectively. CHIP was associated with an increased risk of incident AAA (hazard ratio [HR], 1.21 [95% CI, 1.01-1.44]; P=0.034), with large CHIP clones exhibiting greater effect size (HR, 1.35 [95% CI, 1.10-1.66]; P=0.0045). Driver gene-specific analyses revealed that ASXL1-mediated CHIP exerted the strongest effect size on AAA risk (HR, 2.10 [95% CI, 1.54-2.88]; P<0.001). The presence of 2 IL6R p.Asp358Ala alleles attenuated the risk of AAA in large CHIP carriers (HR, 0.48 [95% CI, 0.23-0.99]; P=0.046). In the joint analysis, participants with CHIP and high genetic risk had a higher risk of developing AAA than those without CHIP and with low genetic risk (HR, 2.15 [95% CI, 1.63-2.85]; P<0.001).</p>
CONCLUSIONS: CHIP is associated with an increased risk of AAA. Genetic IL-6 signaling deficiency attenuates the risk of AAA in large CHIP carriers. CHIP may serve as an attractive target for the prevention and treatment of AAA.</p>
15 Keywords
- Aged
- Aortic Aneurysm, Abdominal
- Clonal Hematopoiesis
- Female
- Genetic Predisposition to Disease
- Humans
- Incidence
- Interleukin-6
- Male
- Middle Aged
- Phenotype
- Receptors, Interleukin-6
- Risk Assessment
- Risk Factors
- United Kingdom
10 Authors
- Yu Tan
- Xuanmeng Zhu
- Yuanfeng Huang
- Chenxuan Zhao
- Xunjie Cheng
- Jinchen Li
- Guogang Zhang
- Tianqi Ma
- Shujun Yang
- Yongping Bai
1 Application
| Application ID | Title |
|---|---|
| 84443 | Lifestyles, Environmental Exposures, and Psychological Factors, and Genetic-Environmental Relationships in Aging-Related Diseases |
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