Understanding the Genetic Basis of Atrial Fibrillation: Towards a Pharmacogenetic Approach for Arrhythmia Treatment

2013 ◽  
pp. 65-75
Author(s):  
Jason D. Roberts ◽  
Michael H. Gollob
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Basis

Monogenic and oligogenic cardiovascular diseases: genetics of arrhythmias—short QT syndrome

2018 ◽  
Author(s):  
Erol Tülümen ◽  
Martin Borggrefe
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Basis ◽  
Association Studies ◽  
Single Gene ◽  
Candidate Gene Approach ◽  
Genome Wide Association Studies ◽  
Loss Of Function ◽  
Short Qt Syndrome ◽  
Dispersion Of Repolarization ◽  
Qt Syndrome

Short QT syndrome (SQTS) is a very rare, sporadic or autosomal dominant inherited channelopathy characterized by abnormally short QT intervals on the electrocardiogram and increased propensity to atrial and ventricular tachyarrhythmias and/or sudden cardiac death. Since its recognition as a distinct clinical entity in 2000, significant progress has been made in defining the clinical, molecular, and genetic basis of SQTS. To date, several causative gain-of-function mutations in potassium channel genes and loss-of-function mutations in calcium channel genes have been identified. The physiological consequence of these mutations is an accelerated repolarization, thus abbreviated action potentials and shortened QT interval with an increased inhomogeneity and dispersion of repolarization. Regarding other rare monogenetic arrhythmias, a genetic basis of atrial fibrillation was considered very unlikely until very recently. However, in the last decade the heritability of atrial fibrillation in the general population has been well described in several epidemiological studies. So far, more than 30 genes have been implicated in atrial fibrillation through candidate gene approach studies, and 14 loci were found to be associated with atrial fibrillation through genome-wide association studies. This genetic heterogeneity and the low prevalence of mutations in any single gene restrict the clinical utility of genetic screening in atrial fibrillation.

Monogenic and oligogenic cardiovascular diseases: genetics of arrhythmias—short QT syndrome

ESC CardioMed ◽  
2018 ◽  
pp. 676-679
Author(s):  
Erol Tülümen ◽  
Martin Borggrefe
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Basis ◽  
Association Studies ◽  
Single Gene ◽  
Epidemiological Studies ◽  
Candidate Gene Approach ◽  
Loss Of Function ◽  
Short Qt Syndrome ◽  
Qt Intervals ◽  
Qt Syndrome

Short QT syndrome (SQTS) is a very rare, sporadic or autosomal dominant inherited channelopathy characterized by abnormally short QT intervals on the electrocardiogram and increased propensity to atrial and ventricular tachyarrhythmias and/or sudden cardiac death. Since its recognition as a distinct clinical entity in 2000, significant progress has been made in defining the clinical, molecular, and genetic basis of SQTS. To date, several causative gain-of-function mutations in potassium channel genes and loss-of-function mutations in calcium channel genes have been identified. The physiological consequence of these mutations is an accelerated repolarization, thus abbreviated action potentials and shortened QT interval with an increased inhomogeneity and dispersion of repolarization. Regarding other rare monogenetic arrhythmias, a genetic basis of atrial fibrillation was considered very unlikely until very recently. However, in the last decade the heritability of atrial fibrillation in the general population has been well described in several epidemiological studies. So far, more than 30 genes have been implicated in atrial fibrillation through candidate gene approach studies, and more than 25 loci were found to be associated with atrial fibrillation through genome-wide association studies. This genetic heterogeneity and the low prevalence of mutations in any single gene restrict the clinical utility of genetic screening in atrial fibrillation.

The molecular genetic basis of atrial fibrillation

2020 ◽  
Vol 139 (12) ◽  
pp. 1485-1498
Author(s):  
Xin Huang ◽  
Yuhui Li ◽  
Junguo Zhang ◽  
Xiaojie Wang ◽  
Ziyi Li ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Basis ◽  
Molecular Genetic ◽  
Molecular Genetic Basis

scholarly journals Genetic basis of atrial fibrillation

2016 ◽  
Vol 3 (4) ◽  
pp. 257-262 ◽  
Author(s):  
Oscar Campuzano ◽  
Alexandra Perez-Serra ◽  
Anna Iglesias ◽  
Ramon Brugada
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Basis

scholarly journals A calcium transport mechanism for atrial fibrillation in Tbx5-mutant mice

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Wenli Dai ◽  
Brigitte Laforest ◽  
Leonid Tyan ◽  
Kaitlyn M Shen ◽  
Rangarajan D Nadadur ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Transcriptional Control ◽  
Genetic Basis ◽  
Calcium Uptake ◽  
Mutant Mice ◽  
Sodium Calcium Exchanger ◽  
Calcium Fluxes ◽  
T Box ◽  
Cellular Ca ◽  
Dependent Pathway

Risk for Atrial Fibrillation (AF), the most common human arrhythmia, has a major genetic component. The T-box transcription factor TBX5 influences human AF risk, and adult-specific Tbx5-mutant mice demonstrate spontaneous AF. We report that TBX5 is critical for cellular Ca2+ homeostasis, providing a molecular mechanism underlying the genetic implication of TBX5 in AF. We show that cardiomyocyte action potential (AP) abnormalities in Tbx5-deficient atrial cardiomyocytes are caused by a decreased sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA2)-mediated SR calcium uptake which was balanced by enhanced trans-sarcolemmal calcium fluxes (calcium current and sodium/calcium exchanger), providing mechanisms for triggered activity. The AP defects, cardiomyocyte ectopy, and AF caused by TBX5 deficiency were rescued by phospholamban removal, which normalized SERCA function. These results directly link transcriptional control of SERCA2 activity, depressed SR Ca2+ sequestration, enhanced trans-sarcolemmal calcium fluxes, and AF, establishing a mechanism underlying the genetic basis for a Ca2+-dependent pathway for AF risk.

scholarly journals Genetic Discoveries in Atrial Fibrillation and Implications for Clinical Practice

2014 ◽  
Vol 3 (2) ◽  
pp. 69 ◽  
Author(s):  
Saagar Mahida ◽  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Genetic Architecture ◽  
Genetic Basis ◽  
Everyday Clinical Practice ◽  
The Past ◽  
Genetics Research ◽  
Genotyping Technology

Atrial fibrillation (AF) is an arrhythmia with a genetic basis. Over the past decade, rapid advances in genotyping technology have revolutionised research regarding the genetic basis of AF. While AF genetics research was previously largely restricted to familial forms of AF, recent studies have begun to characterise the genetic architecture underlying the form of AF encountered in everyday clinical practice. These discoveries could have a significant impact on the management of AF. However, much work remains before genetic findings can be translated to clinical practice. This review summarises results of studies in AF genetics to date and discusses the potential implications of these findings in clinical practice.

Complex cardiovascular diseases: genetic determinants of atrial fibrillation

ESC CardioMed ◽  
2018 ◽  
pp. 730-732
Author(s):  
Patrick T. Ellinor ◽  
Steven A. Lubitz
Keyword(s):  
Atrial Fibrillation ◽  
Cardiovascular Diseases ◽  
Genetic Basis ◽  
Genetic Determinants ◽  
The Past ◽  
Comprehensive Picture ◽  
Future Work ◽  
Made In

Great strides have been made in the past decade in our understanding of the genetic basis of atrial fibrillation. We have come to appreciate that atrial fibrillation is heritable and that familial forms of atrial fibrillation are rare. In the next 2 years, we can expect to have a comprehensive picture of the genes underlying atrial fibrillation. Future work will be focused on understanding the function of these atrial fibrillation-related genes, and in translating these findings back into the clinical realm.

scholarly journals New Advances in the Genetic Basis of Atrial Fibrillation

2012 ◽  
Vol 23 (12) ◽  
pp. 1400-1406 ◽  
Author(s):  
SAAGAR MAHIDA ◽  
PATRICK T. ELLINOR
Keyword(s):  
Atrial Fibrillation ◽  
Genetic Basis
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