한빛사논문
- 조회357
Hyo-Jeong Ahn1†, Hong Yul An2†, Gangpyo Ryu3,4, Jiwoo Lim2, Choonghyun Sun2, Han Song2, Su-Yeon Choi5,6, Heesun Lee5,6, Taylor Maurer3, Daniel Nachun3, Soonil Kwon1, So-Ryoung Lee1,5, Gregory Y. H. Lip7,8, Seil Oh1,5, Siddhartha Jaiswal3*, Youngil Koh1,2,4,9*, and Eue-Keun Choi1,5*
1Department of Internal Medicine, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea;
2Genome Opinion Incorporation, Seoul 04799, Republic of Korea;
3Department of Pathology, Stanford University School of Medicine, Stanford, CA 94305, USA;
4Cancer Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea;
5Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea;
6Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center, Seoul, Korea;
7Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University, Liverpool Chest and Heart Hospital, Liverpool, UK;
8Danish Center for Health Services Research, Department of Clinical Medicine, Aalborg University, Aalborg, Denmark; and
9Biomedical Research Institute, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Republic of Korea
* Corresponding authors: Siddhartha Jaiswal, Youngil Koh, and Eue-Keun Choi
† The first two authors contributed equally to the study.
Abstract
Background and aims: Both clonal haematopoiesis of indeterminate potential (CHIP) and atrial fibrillation (AF) are age-related conditions. This study investigated the potential role of CHIP in the development and progression of AF.
Methods: Deep-targeted sequencing of 24 CHIP mutations (a mean depth of coverage = 1000×) was performed in 1004 patients with AF and 3341 non-AF healthy subjects. Variant allele fraction ≥ 2.0% indicated the presence of CHIP mutations. The association between CHIP and AF was evaluated by the comparison of (i) the prevalence of CHIP mutations between AF and non-AF subjects and (ii) clinical characteristics discriminated by CHIP mutations within AF patients. Furthermore, the risk of clinical outcomes-the composite of heart failure, ischaemic stroke, or death-according to the presence of CHIP mutations in AF was investigated from the UK Biobank cohort.
Results: The mean age was 67.6 ± 6.9 vs. 58.5 ± 6.5 years in AF (paroxysmal, 39.0%; persistent, 61.0%) and non-AF cohorts, respectively. CHIP mutations with a variant allele fraction of ≥2.0% were found in 237 (23.6%) AF patients (DNMT3A, 13.5%; TET2, 6.6%; and ASXL1, 1.5%) and were more prevalent than non-AF subjects [356 (10.7%); P < .001] across the age. After multivariable adjustment (age, sex, smoking, body mass index, diabetes, and hypertension), CHIP mutations were 1.4-fold higher in AF [adjusted odds ratio (OR) 1.38; 95% confidence interval 1.10-1.74, P < .01]. The ORs of CHIP mutations were the highest in the long-standing persistent AF (adjusted OR 1.50; 95% confidence interval 1.14-1.99, P = .004) followed by persistent (adjusted OR 1.44) and paroxysmal (adjusted OR 1.33) AF. In gene-specific analyses, TET2 somatic mutation presented the highest association with AF (adjusted OR 1.65; 95% confidence interval 1.05-2.60, P = .030). AF patients with CHIP mutations were older and had a higher prevalence of diabetes, a longer AF duration, a higher E/E', and a more severely enlarged left atrium than those without CHIP mutations (all P < .05). In UK Biobank analysis of 21 286 AF subjects (1297 with CHIP and 19 989 without CHIP), the CHIP mutation in AF is associated with a 1.32-fold higher risk of a composite clinical event (heart failure, ischaemic stroke, or death).
Conclusions: CHIP mutations, primarily DNMT3A or TET2, are more prevalent in patients with AF than non-AF subjects whilst their presence is associated with a more progressive nature of AF and unfavourable clinical outcomes.
논문정보
- Research article
- 2024년 01월 (BRIC 등록일 2024-01-18)
- 국내(교신)+국외 연구진
- 의약학 > 응용의학
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