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GAREM1 regulates the PR interval on electrocardiograms.
Hye Ok Kim1, Ji Eun Lim1, Myung Jun Kim1
1Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, 26, Kyunghee-daero, Dongdaemun-gu, Seoul, 02447, Korea.
Journal of Human Genetics
|December 24, 2017
Summary
The gene GAREM1 is linked to the PR interval, a measure of heart rhythm on electrocardiograms (ECGs). Reducing Garem1 in mice altered heart rhythm, suggesting GAREM1 as a potential therapeutic target for heart conditions.
Area of Science:
- Genetics and Cardiovascular Physiology
- Molecular Biology and Electrophysiology
Background:
- The PR interval on electrocardiograms (ECGs) reflects cardiac conduction time.
- A prior genomewide association study (GWAS) implicated GAREM1 in regulating the PR interval.
Purpose of the Study:
- To validate the association between GAREM1 and the PR interval in an independent cohort.
- To investigate the functional role of Garem1 in cardiac electrophysiology using a mouse model.
Main Methods:
- Meta-analysis of ECG data from 5646 individuals across two Korean cohorts to assess the association of a GAREM1 variant (rs17744182) with PR interval.
- In vivo knockdown of Garem1 expression in mice using Garem1 siRNA.
- Assessment of Garem1 transcript levels in cardiac atria, PR interval measurements in mice, and immunohistological analysis of Garem1 expression in the heart.
Main Results:
- A significant genomewide association was found between the GAREM1 variant rs17744182 and the PR interval (P = 2.39 × 10⁻⁸).
- Garem1 siRNA injection significantly reduced Garem1 transcript levels in mouse atria by 53% (P = 0.029).
- Mice with reduced Garem1 expression exhibited a significant decrease in PR interval compared to controls (43.27 ms vs. 44.89 ms, P = 0.007).
- Garem1 was specifically expressed in intracardiac ganglia neurons, including cholinergic and adrenergic cells.
Conclusions:
- GAREM1 is functionally involved in regulating the PR interval of ECGs.
- These findings highlight the role of Garem1 within intracardiac ganglia of the autonomic nervous system in heart rhythm regulation.
- GAREM1 represents a potential therapeutic target for managing cardiac rhythm disorders like atrial fibrillation.
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