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. 2024 Dec;113(12):1733-1744.
doi: 10.1007/s00392-024-02446-x. Epub 2024 Apr 18.

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

Roman Tremmel  1   2 , Valeria Martínez Pereyra  3 , Incifer Broders  3 , Elke Schaeffeler  1   2 , Per Hoffmann  4   5 , Markus M Nöthen  4   6 , Raffi Bekeredjian  3 , Udo Sechtem  3 , Matthias Schwab  1   7   2 , Peter Ong  8
Affiliations

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

Roman Tremmel et al. Clin Res Cardiol. 2024 Dec.

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.

Keywords: Cardiac biomarker; Cardiovascular; Coronary artery spasm; Endothelin-1; Genetic variants.

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Conflict of interest statement

Declarations. 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. Conflict of interest: The authors declare no competing interests.

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