A functional variant in the promoter region regulates the C-reactive protein gene and is a potential candidate for increased risk of atrial fibrillation

Journal of Internal Medicine
S-N ChangJ-J Hwang

Abstract

In a large population-based cohort, the level of C-reactive protein (CRP) in patients at baseline predicts an increased risk of future development of atrial fibrillation (AF). The mechanism of this increased risk is unknown. Furthermore, both the molecular effects of CRP on atrial myocytes and fibroblasts and whether genetic variants in the CRP gene predispose to AF are also unknown. A genetic association study between CRP gene polymorphisms and AF was performed in two independent populations (I: 100 AF patients and 101 controls; II: 348 AF patients and 356 controls), with functional studies to elucidate the mechanism of association. Three polymorphisms (T-861C, A-821G and C-390A/C-390T) were found in the 1-kb promoter of CRP. A triallelic polymorphism (C-390A/C-390T) captured all haplotype information and determined the CRP gene promoter activity and the plasma CRP level, and was in nearly complete linkage disequilibrium with G1059C polymorphism in exon 2. The -390A variant was associated with a higher CRP gene promoter activity, a higher plasma CRP level and a higher risk of AF. Patients with AF also had a higher plasma CRP level than controls. CRP significantly increased the inward L-type calcium current in atrial myocytes w...Continue Reading

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Citations

Nov 27, 2014·Texas Heart Institute Journal·Roberto GaleaLuigi M Biasucci
Feb 11, 2015·International Journal of Cardiology·Zhurong LuoMingfang Huang
Jul 9, 2016·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Hui JiangYinglong Hou
Apr 27, 2018·Innovations : Technology and Techniques in Cardiothoracic and Vascular Surgery·Niels J VerberkmoesAlbert H M van Straten
Oct 13, 2017·Current Medicinal Chemistry·Christos GeorgakopoulosDimitrios Tousoulis

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