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Genetic associations of cardiovascular risk genes in European patients with coronary artery spasm

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Abstract

Background

Coronary artery spasm (CAS) is a frequent finding in patients presenting with angina pectoris. Although the pathogenesis of CAS is incompletely understood, previous studies suggested a genetic contribution. Our study aimed to elucidate genetic variants in a cohort of European patients with angina and unobstructed coronary arteries who underwent acetylcholine (ACh) provocation testing.

Methods

A candidate association analysis of 208 genes previously associated with cardiovascular conditions was performed using genotyped and imputed variants in patients grouped in epicardial (focal, diffuse) CAS (n = 119) and microvascular CAS (n = 87). Patients with a negative ACh test result (n = 45) served as controls.

Results

We found no association below the genome-wide significance threshold of p < 5 × 10−8, thus not confirming variants in ALDH2, NOS3, and ROCK2 previously reported in CAS patients of Asian ancestry. However, the analysis identified suggestive associations (p < 10−05) for the groups of focal epicardial CAS (CDH13) and diffuse epicardial CAS (HDAC9, EDN1). Downstream analysis of the potential EDN1 risk locus showed that CAS patients have significantly increased plasma endothelin-1 levels (ET-1) compared to controls. An EDN1 haplotype comprising rs9349379 and rs2070698 was significantly associated to ET-1 levels (p = 0.01).

Conclusions

In summary, we suggest EDN1 as potential genetic risk loci for patients with diffuse epicardial CAS, and European ancestry. Plasma ET-1 levels may serve as a potential cardiac marker.

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Data availability

The dataset analyzed during the current study is available from the corresponding author upon reasonable request.

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Funding

This study was supported by a grant from the German Heart Foundation (FF19/290), the Berthold-Leibinger-Foundation, Ditzingen, Germany, and the Robert Bosch Stiftung, Stuttgart, Germany.

Author information

Authors and Affiliations

  1. Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology, Stuttgart, Germany

    Roman Tremmel, Elke Schaeffeler & Matthias Schwab

  2. Department of Cardiology and Angiology, Robert-Bosch-Hospital, Auerbachstr. 110, 70376, Stuttgart, Germany

    Valeria Martínez Pereyra, Incifer Broders, Raffi Bekeredjian, Udo Sechtem & Peter Ong

  3. Institute of Human Genetics, University of Bonn, Bonn, Germany

    Per Hoffmann & Markus M. Nöthen

  4. Division of Medical Genetics, Department of Biomedicine, University of Basel, Basel, Switzerland

    Per Hoffmann

  5. Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany

    Markus M. Nöthen

  6. Departments of Clinical Pharmacology, and Pharmacy and Biochemistry, University of Tübingen, Tübingen, Germany

    Matthias Schwab

  7. University of Tübingen, Tübingen, Germany

    Roman Tremmel, Elke Schaeffeler & Matthias Schwab

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  1. Roman Tremmel
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Correspondence to Peter Ong.

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Ethical approval

Approval was obtained from the ethics committee at the Landesärztekammer Baden-Württemberg, Stuttgart, Germany. The procedures used in this study adhere to the tenets of the Declaration of Helsinki. All study participants provided written informed consent.

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Tremmel, R., Martínez Pereyra, V., Broders, I. et al. Genetic associations of cardiovascular risk genes in European patients with coronary artery spasm. Clin Res Cardiol (2024). https://doi.org/10.1007/s00392-024-02446-x

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