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Int. J. Mol. Sci. 2018, 19(1), 295; doi:10.3390/ijms19010295

Differential Association of Cx37 and Cx40 Genetic Variants in Atrial Fibrillation with and without Underlying Structural Heart Disease

1
Service of General Internal medicine, University Hospitals of Geneva, 1211 Geneva, Switzerland
2
Department of Pathology and Immunology, University of Geneva, 1211 Geneva, Switzerland
3
Service of Cardiology, University Hospitals of Geneva, 1211 Geneva, Switzerland
4
Service of Endocrinology and Diabetes, University Hospitals of Geneva, 1211 Geneva, Switzerland
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 19 December 2017 / Revised: 12 January 2018 / Accepted: 16 January 2018 / Published: 19 January 2018
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Abstract

Atrial fibrillation (AF) appears in the presence or absence of structural heart disease. The majority of foci causing AF are located near the ostia of pulmonary veins (PVs), where cardiomyocytes and vascular smooth muscle cells interdigitate. Connexins (Cx) form gap junction channels and participate in action potential propagation. Genetic variants in genes encoding Cx40 and Cx37 affect their expression or function and may contribute to PV arrhythmogenicity. DNA was obtained from 196 patients with drug-resistant, symptomatic AF with and without structural heart disease, who were referred for percutaneous catheter ablation. Eighty-nine controls were matched for age, gender, hypertension, and BMI. Genotyping of the Cx40 −44G > A, Cx40 +71A > G, Cx40 −26A > G, and Cx37 1019C > T polymorphisms was performed. The promoter A Cx40 polymorphisms (−44G > A and +71A > G) showed no association with non-structural or structural AF. Distribution of the Cx40 promoter B polymorphism (−26A > G) was different in structural AF when compared to controls (p = 0.03). There was no significant difference with non-structural AF (p = 0.50). The distribution of the Cx37 1019C > T polymorphism was different in non-structural AF (p = 0.03) but not in structural AF (p = 0.08) when compared to controls. Our study describes for the first time an association of drug-resistant non-structural heart disease AF with the Cx37 1019C > T gene polymorphism. We also confirmed the association of the Cx40 − 26G > A polymorphism in patients with AF and structural disease. View Full-Text
Keywords: atrial fibrillation; connexin; polymorphism; genetic variant atrial fibrillation; connexin; polymorphism; genetic variant
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MDPI and ACS Style

Carballo, S.; Pfenniger, A.; Carballo, D.; Garin, N.; James, R.W.; Mach, F.; Shah, D.; Kwak, B.R. Differential Association of Cx37 and Cx40 Genetic Variants in Atrial Fibrillation with and without Underlying Structural Heart Disease. Int. J. Mol. Sci. 2018, 19, 295.

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