Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124)
Associated with Coronary Artery Affliction in Patients with
Severe Arrhythmias

J 2024

Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124) Associated with Coronary Artery Affliction in Patients with Severe Arrhythmias

VAŠKŮ, Anna, Tomáš NOVOTNÝ and Jindřich ŠPINAR

Basic information

Original name

Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124) Associated with Coronary Artery Affliction in Patients with Severe Arrhythmias

Authors

VAŠKŮ, Anna (203 Czech Republic, belonging to the institution), Tomáš NOVOTNÝ (203 Czech Republic, belonging to the institution) and Jindřich ŠPINAR (203 Czech Republic, belonging to the institution)

Edition

GENES, BASEL, MDPI, 2024, 2073-4425

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30201 Cardiac and Cardiovascular systems

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.500 in 2022

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/genes15020200

UT WoS

001175083200001

Keywords in English

coronary artery disease; arrhythmia; SCN5A

Abstract

V originále

Several mutations in this gene for the alpha subunit of the cardiac sodium channel have been identified in a heterogeneous subset of cardiac rhythm syndromes, including Brugada syndrome, progressive cardiac conduction defect, sick sinus node syndrome, atrial fibrillation and dilated cardiomyopathy. The aim of our study was to associate some SCN5A polymorphic variants directly with confirmed coronary stenoses in patients with non-LQTS ventricular fibrillation/flutter treated by an implantable cardioverter defibrillator. Materials and Methods: A group of 32 unrelated individuals, aged 63 +/- 12 years, was included in the study. All the patients were examined, diagnosed and treated with an implantable cardioverter defibrillator at the Department of Internal Cardiology Medicine, Faculty Hospital Brno. The control group included 87 persons of similar age without afflicted coronary circulation, which was confirmed coronagraphically. Genomic DNA was extracted from samples of peripheral blood according to the standard protocol. Two SCN5A polymorphisms-IVS9-3C/A (rs41312433) and A1673G (rs1805124, H558R)-were examined in association with coronary artery stenosis in the patients. Results: In the case-control study, no significant differences in genotype distribution/allelic frequencies were observed for IVS9-3c>a and A1673G gene polymorphisms between patients with severe arrhythmias and healthy persons. The distribution of SCN5A double genotypes was not significantly different among different types of arrhythmias according to their ejection fraction in arrhythmic patients (p = 0.396). The ventricular arrhythmias with an ejection fraction below 40% were found to be 10.67 times more frequent in patients with multiple coronary stenosis with clinically valid sensitivity, specificity and power tests. In the genotype-phenotype study, we observed a significant association of both SCN5A polymorphisms with the stenosis of coronary vessels in the patients with severe arrhythmia. The double genotype of polymorphisms IVS9-3C/A together with A1673G (CCAA) as well as their simple genotypes were associated with significant multiple stenosis of coronary arteries (MVS) with high sensitivity and specificity (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.70; specificity 0.682; power test 0.359) Moreover, when a concrete stenotic coronary artery was associated with SCN5A genotypes, the CCAA double genotype was observed to be five times more frequent in patients with significant stenosis in the right coronary artery (RCA) compared to those without affliction of this coronary artery (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.682; specificity 0.700; power test 0.359). The CCAA genotype was also more frequent in patients without RCA affliction with MVS (p = 0.008); in patients with ACD affliction but without MVS (p = 0.008); and in patients with both ACD affliction and MVS compared to those without ACD affliction and MVS (p = 0.005). Conclusions: Our study presents a highly sensitive and specific association of two polymorphisms in SCN5A with significant coronary artery stenoses in patients with potentially fatal ventricular arrhythmias. At the same time, these polymorphisms were not associated with arrhythmias themselves. Thus, SCN5A gene polymorphic variants may form a part of germ cell gene predisposition to ischemia.

Citovat

VAŠKŮ, Anna, Tomáš NOVOTNÝ and Jindřich ŠPINAR. Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124) Associated with Coronary Artery Affliction in Patients with Severe Arrhythmias. GENES. BASEL: MDPI, 2024, vol. 15, No 2, p. 1-10. ISSN 2073-4425. Available from: https://dx.doi.org/10.3390/genes15020200.

@article{2398797,
   author = {Vašků, Anna and Novotný, Tomáš and Špinar, Jindřich},
   article_location = {BASEL},
   article_number = {2},
   doi = {http://dx.doi.org/10.3390/genes15020200},
   keywords = {coronary artery disease; arrhythmia; SCN5A},
   language = {eng},
   issn = {2073-4425},
   journal = {GENES},
   title = {Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124) Associated with Coronary Artery Affliction in Patients with Severe Arrhythmias},
   url = {https://www.mdpi.com/2073-4425/15/2/200},
   volume = {15},
   year = {2024}
}

TY  - JOUR
ID  - 2398797
AU  - Vašků, Anna - Novotný, Tomáš - Špinar, Jindřich
PY  - 2024
TI  - Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124) Associated with Coronary Artery Affliction in Patients with Severe Arrhythmias
JF  - GENES
VL  - 15
IS  - 2
SP  - 1-10
EP  - 1-10
PB  - MDPI
SN  - 20734425
KW  - coronary artery disease
KW  - arrhythmia
KW  - SCN5A
UR  - https://www.mdpi.com/2073-4425/15/2/200
N2  - Several mutations in this gene for the alpha subunit of the cardiac sodium channel have been identified in a heterogeneous subset of cardiac rhythm syndromes, including Brugada syndrome, progressive cardiac conduction defect, sick sinus node syndrome, atrial fibrillation and dilated cardiomyopathy. The aim of our study was to associate some SCN5A polymorphic variants directly with confirmed coronary stenoses in patients with non-LQTS ventricular fibrillation/flutter treated by an implantable cardioverter defibrillator. Materials and Methods: A group of 32 unrelated individuals, aged 63 +/- 12 years, was included in the study. All the patients were examined, diagnosed and treated with an implantable cardioverter defibrillator at the Department of Internal Cardiology Medicine, Faculty Hospital Brno. The control group included 87 persons of similar age without afflicted coronary circulation, which was confirmed coronagraphically. Genomic DNA was extracted from samples of peripheral blood according to the standard protocol. Two SCN5A polymorphisms-IVS9-3C/A (rs41312433) and A1673G (rs1805124, H558R)-were examined in association with coronary artery stenosis in the patients. Results: In the case-control study, no significant differences in genotype distribution/allelic frequencies were observed for IVS9-3c>a and A1673G gene polymorphisms between patients with severe arrhythmias and healthy persons. The distribution of SCN5A double genotypes was not significantly different among different types of arrhythmias according to their ejection fraction in arrhythmic patients (p = 0.396). The ventricular arrhythmias with an ejection fraction below 40% were found to be 10.67 times more frequent in patients with multiple coronary stenosis with clinically valid sensitivity, specificity and power tests. In the genotype-phenotype study, we observed a significant association of both SCN5A polymorphisms with the stenosis of coronary vessels in the patients with severe arrhythmia. The double genotype of polymorphisms IVS9-3C/A together with A1673G (CCAA) as well as their simple genotypes were associated with significant multiple stenosis of coronary arteries (MVS) with high sensitivity and specificity (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.70; specificity 0.682; power test 0.359) Moreover, when a concrete stenotic coronary artery was associated with SCN5A genotypes, the CCAA double genotype was observed to be five times more frequent in patients with significant stenosis in the right coronary artery (RCA) compared to those without affliction of this coronary artery (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.682; specificity 0.700; power test 0.359). The CCAA genotype was also more frequent in patients without RCA affliction with MVS (p = 0.008); in patients with ACD affliction but without MVS (p = 0.008); and in patients with both ACD affliction and MVS compared to those without ACD affliction and MVS (p = 0.005). Conclusions: Our study presents a highly sensitive and specific association of two polymorphisms in SCN5A with significant coronary artery stenoses in patients with potentially fatal ventricular arrhythmias. At the same time, these polymorphisms were not associated with arrhythmias themselves. Thus, SCN5A gene polymorphic variants may form a part of germ cell gene predisposition to ischemia.
ER  -

VAŠKŮ, Anna, Tomáš NOVOTNÝ and Jindřich ŠPINAR. Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124) Associated with Coronary Artery Affliction in Patients with Severe Arrhythmias. \textit{GENES}. BASEL: MDPI, 2024, vol.~15, No~2, p.~1-10. ISSN~2073-4425. Available from: https://dx.doi.org/10.3390/genes15020200.

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