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Atrial Fibrillation Genes

Mehrnaz Riazian, Elnaz Khorrami, Elham Alipoor, Sina Moradmand, Mehdi Yaseri, Mohammad Javad Hosseinzadeh-Attar
BACKGROUND: Apelin, the endogenous ligand of orphan receptor APJ (gene symbol APLNR), is an adipokine that was suggested to have a direct correlation with obesity. This peptide might play a role in obesity-related disorders, especially in the cardiovascular system. Currently, few data are available on levels and potential metabolic functions of apelin in different cardiac diseases including atrial fibrillation (AF) and coronary artery disease (CAD), which have common underlying pathophysiological mechanisms...
October 2016: American Journal of the Medical Sciences
Wenjun Jia, Xin Qi, Qi Li
BACKGROUND Atrial fibrillation (AF) is the most common sustained arrhythmia affected by multiple cardiovascular risk factors. It is reported that caveolin-1 gene (CAV1) rs3807989 polymorphism might be associated with AF risk. The goal of this meta-analysis was to confirm the association between CAV1 rs3807989 polymorphism and susceptibility to AF. MATERIAL AND METHODS We carried out a comprehensive literature search through the electronic databases PubMed, MEDLIN, and Web of Science. We performed a meta-analysis of all selected studies based on CAV1 rs3807989 polymorphism genotypes, including 3758 cases and 6126 controls...
October 24, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
Fahima Syeda, Andrew P Holmes, Ting Y Yu, Samantha Tull, Stefan Michael Kuhlmann, Davor Pavlovic, Daniel Betney, Genna Riley, Jan P Kucera, Florian Jousset, Joris R de Groot, Stephan Rohr, Nigel A Brown, Larissa Fabritz, Paulus Kirchhof
BACKGROUND: Antiarrhythmic drugs are widely used to treat patients with atrial fibrillation (AF), but the mechanisms conveying their variable effectiveness are not known. Recent data suggested that paired like homeodomain-2 transcription factor (PITX2) might play an important role in regulating gene expression and electrical function of the adult left atrium (LA). OBJECTIVES: After determining LA PITX2 expression in AF patients requiring rhythm control therapy, the authors assessed the effects of Pitx2c on LA electrophysiology and the effect of antiarrhythmic drugs...
October 25, 2016: Journal of the American College of Cardiology
Nathan R Tucker, Saagar Mahida, Jiangchuan Ye, Elizabeth J Abraham, Julie A Mina, Victoria A Parsons, Michael A McLellan, Marisa A Shea, Alan Hanley, Emelia J Benjamin, David J Milan, Honghuang Lin, Patrick T Ellinor
BACKGROUND: The genetic basis of atrial fibrillation (AF) and congenital heart disease remains incompletely understood. OBJECTIVE: We sought to determine the causative mutation in a family with AF, atrial septal and ventricular septal defects. METHODS: We evaluated a pedigree with 16 family members, one with an atrial septal defect, one with a ventricular septal defect and three with AF; we performed whole exome sequencing in three affected family members...
October 15, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Satoshi Umemura
Primary aldosteronism (PA) is a heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most frequent endocrine cause of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential hypertension.Here I review the recent progress in understanding of the genetic and molecular mechanisms leading to autonomous aldosterone production in PA.Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with resistant hypertension...
September 2016: Journal of Hypertension
Daniel F Gudbjartsson, Hilma Holm, Patrick Sulem, Gisli Masson, Asmundur Oddsson, Olafur Th Magnusson, Jona Saemundsdottir, Hafdis Th Helgadottir, Hannes Helgason, Hrefna Johannsdottir, Solveig Gretarsdottir, Sigurjon A Gudjonsson, Inger Njølstad, Maja-Lisa Løchen, Larry Baum, Ronald C W Ma, Gunnlaugur Sigfusson, Augustine Kong, Guðmundur Thorgeirsson, Jon Th Sverrisson, Unnur Thorsteinsdottir, Kari Stefansson, David O Arnar
AIMS: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in man, causing substantial morbidity and mortality with a major worldwide public health impact. It is increasingly recognized as a highly heritable condition. This study aimed to determine genetic risk factors for early-onset AF. METHODS AND RESULTS: We sequenced the whole genomes of 8453 Icelanders and imputed genotypes of the 25.5 million sequence variants we discovered into 1799 Icelanders with early-onset AF (diagnosed before 60 years of age) and 337 453 controls...
October 14, 2016: European Heart Journal
Lars Folkestad, Jannie Dahl Hald, Jeppe Gram, Bente L Langdahl, Anne Pernille Hermann, Axel Cp Diederichsen, Bo Abrahamsen, Kim Brixen
BACKGROUND: Osteogenesis imperfecta (OI) is a hereditary connective tissue disease often due to mutations in genes coding for type 1 collagen. Collagen type 1 is important in the development of the heart and vasculature. Little is known about the risk of cardiovascular disease (CVD) in OI. OBJECTIVE: To investigate the risk of symptomatic CVD in OI. DESIGN: A Danish nationwide, population-based and register-based longitudinal open cohort study...
September 30, 2016: International Journal of Cardiology
Yu-Feng Hu, Hsueh-Hsiao Wang, Hung-I Yeh, Kun-Tai Lee, Yenn-Jiang Lin, Shih-Lin Chang, Li-Wei Lo, Ta-Chuan Tuan, Cheng-Hung Li, Tze-Fan Chao, Fa-Po Chung, Jo-Nan Liao, Paul Wei Hua Tang, Wei-Chung Tsai, Chuen-Wang Chiou, Shih-Ann Chen
BACKGROUND: The association of gene variants with atrial fibrillation (AF) type and the recurrence of AF after catheter ablation in Taiwan is still unclear. In this study, we aimed to investigate the relationships between gene variants, AF type, and the recurrence of AF. METHODS: In our investigation, we examined 383 consecutive patients with AF (61.9 ± 14.0 years; 63% men); of these 383 patients, 189 underwent catheter ablation for drug-refractory AF. Thereafter, the single nucleotide polymorphisms rs2200733, and rs7193343 were genotyped using real-time polymerase chain reaction...
September 2016: Acta Cardiol Sin
Dmitriy Alexeyevich Sychev, Aleksandr Vladimirovich Rozhkov, Ruslan Evgenyevich Kazakov, Anna Viktorovna Ananichuk
BACKGROUND: Oral anticoagulants are commonly used to treat patients with thromboembolic pathology. Genetic variations could influence personal response to anticoagulant drugs. Acenocoumarol (AC) is a vitamin K antagonist used in anticoagulant therapy and as a prophylaxis measure in Europe. In this study, we assessed the effect of CYP4F2 rs2108622, ABCB1, and GGCX polymorphisms on the safety profile and regime dosing of AC in patients with nonvalvular atrial fibrillation. METHODS: Fifty patients aged 40-70 years were included...
September 1, 2016: Drug Metabolism and Personalized Therapy
Sarah L Turley, Kerry E Francis, Denise K Lowe, William D Cahoon
Control of ventricular rate is recommended for patients with paroxysmal, persistent, or permanent atrial fibrillation (AF). Existing rate-control options, including beta-blockers, nondihydropyridine calcium channel blockers, and digoxin, are limited by adverse hemodynamic effects and their ability to attain target heart rate (HR). Ivabradine, a novel HR-controlling agent, decreases HR through deceleration of conduction through If ('funny') channels, and is approved for HR reduction in heart failure patients with ejection fraction less than 35% and elevated HR, despite optimal pharmacological treatment...
September 22, 2016: Therapeutic Advances in Cardiovascular Disease
Satoshi Umemura
Primary aldosteronism (PA) is a heterogeneous group of disorders including both sporadic and familial forms (familial hyperaldosteronism type I, II and III). PA is the most frequent endocrine cause of secondary hypertension and associated with a higher rate of cardiovascular complications, compared with essential hypertension.Here I review the recent progress in understanding of the genetic and molecular mechanisms leading to autonomous aldosterone production in PA.Systematic screening detects primary aldosteronism in 5 to 10% of all patients with hypertension and in approximately 20% of patients with resistant hypertension...
September 2016: Journal of Hypertension
Christian Paludan-Müller, Jesper H Svendsen, Morten S Olesen
This review focuses on the genetic basis of atrial fibrillation (AF) and the role of variants in the susceptibility of developing the disease. AF is the most common cardiac arrhythmia affecting 1-2% of the general population. Studies in the last decade have demonstrated that AF, and in particular lone AF, has a substantial genetic component. A number of genome-wide association studies (GWAS) have indicated that common genetic variants, more precisely the so called single-nucleotide polymorphisms (SNPs) are associated with AF...
August 26, 2016: Journal of Electrocardiology
Patrick Lugenbiel, Patrick A Schweizer, Hugo A Katus, Dierk Thomas
The clinical management of heart rhythm disorders still constitutes a major challenge. The development of alternatives to current approaches is of significant interest in order to establish more effective therapies that increase quality of life and reduce symptoms and hospitalizations. Over the past two decades the mechanistic understanding of pathophysiological pathways underlying cardiac arrhythmias has advanced profoundly, opening up novel avenues for mechanism-based therapeutic approaches. In particular, gene therapy offers greater selectivity than small molecule-based or interventional treatment...
September 2, 2016: European Journal of Pharmacology
Steven A Lubitz, Jennifer A Brody, Nathan A Bihlmeyer, Carolina Roselli, Lu-Chen Weng, Ingrid E Christophersen, Alvaro Alonso, Eric Boerwinkle, Richard A Gibbs, Joshua C Bis, L Adrienne Cupples, Peter J Mohler, Deborah A Nickerson, Donna Muzny, Marco V Perez, Bruce M Psaty, Elsayed Z Soliman, Nona Sotoodehnia, Kathryn L Lunetta, Emelia J Benjamin, Susan R Heckbert, Dan E Arking, Patrick T Ellinor, Honghuang Lin
Atrial fibrillation (AF) is a morbid and heritable arrhythmia. Over 35 genes have been reported to underlie AF, most of which were described in small candidate gene association studies. Replication remains lacking for most, and therefore the contribution of coding variation to AF susceptibility remains poorly understood. We examined whole exome sequencing data in a large community-based sample of 1,734 individuals with and 9,423 without AF from the Framingham Heart Study, Cardiovascular Health Study, Atherosclerosis Risk in Communities Study, and NHLBI-GO Exome Sequencing Project and meta-analyzed the results...
September 2016: PLoS Genetics
M Liu, K-C Yang, S C Dudley
The cardiac Na(+) channel (Nav1.5) conducts a depolarizing inward Na(+) current that is responsible for the generation of the upstroke Phase 0 of the action potential. In heart tissue, changes in Na(+) currents can affect conduction velocity and impulse propagation. The cardiac Nav1.5 is also involved in determination of the action potential duration, since some channels may reopen during the plateau phase, generating a persistent or late inward current. Mutations of cardiac Nav1.5 can induce gain or loss of channel function because of an increased late current or a decrease of peak current, respectively...
2016: Current Topics in Membranes
Rangarajan D Nadadur, Michael T Broman, Bastiaan Boukens, Stefan R Mazurek, Xinan Yang, Malou van den Boogaard, Jenna Bekeny, Margaret Gadek, Tarsha Ward, Min Zhang, Yun Qiao, James F Martin, Christine E Seidman, Jon Seidman, Vincent Christoffels, Igor R Efimov, Elizabeth M McNally, Christopher R Weber, Ivan P Moskowitz
Cardiac rhythm is extremely robust, generating 2 billion contraction cycles during the average human life span. Transcriptional control of cardiac rhythm is poorly understood. We found that removal of the transcription factor gene Tbx5 from the adult mouse caused primary spontaneous and sustained atrial fibrillation (AF). Atrial cardiomyocytes from the Tbx5-mutant mice exhibited action potential abnormalities, including spontaneous depolarizations, which were rescued by chelating free calcium. We identified a multitiered transcriptional network that linked seven previously defined AF risk loci: TBX5 directly activated PITX2, and TBX5 and PITX2 antagonistically regulated membrane effector genes Scn5a, Gja1, Ryr2, Dsp, and Atp2a2 In addition, reduced Tbx5 dose by adult-specific haploinsufficiency caused decreased target gene expression, myocardial automaticity, and AF inducibility, which were all rescued by Pitx2 haploinsufficiency in mice...
August 31, 2016: Science Translational Medicine
Takanori Yaegashi, Takeshi Kato, Soichiro Usui, Naomi Kanamori, Hiroshi Furusho, Shin-Ichiro Takashima, Hisayoshi Murai, Shuichi Kaneko, Masayuki Takamura
BACKGROUND: Atrial fibrillation (AF) activates the coagulation system, leading to hypercoagulation of the blood. The liver is a major source of prothrombotic molecules. OBJECTIVE: This study aimed to clarify whether cardiohepatic interactions are involved in AF-related hypercoagulation. METHODS: We compared gene expression profiles of human liver tissue between patients with AF and sinus rhythm. An AF model was created by rapid atrial pacing (RAP) at a frequency of 1200 beats/min in anesthetized 10-week-old Sprague-Dawley rats...
August 26, 2016: Heart Rhythm: the Official Journal of the Heart Rhythm Society
Isik Turker, Takeru Makiyama, Matteo Vatta, Hideki Itoh, Takeshi Ueyama, Akihiko Shimizu, Tomohiko Ai, Minoru Horie
BACKGROUND: Class IC antiarrhythmic agents may induce acquired forms of Brugada Syndrome. We have identified a novel mutation in SCN5A, the gene that encodes the α-subunit of the human cardiac sodium channel (hNav1.5), in a patient who exhibited Brugada- type ECG changes during pharmacotherapy of atrial arrhythmias. OBJECTIVE: To assess whether the novel mutation p.V1328M can cause drug induced Brugada Syndrome. METHODS: Administration of pilsicainide, a class IC antiarrhythmic agent, caused Brugada- type ST elevation in a 66-year-old Japanese male who presented with paroxysmal atrial fibrillation (PAF), type I atrial flutter and inducible ventricular fibrillation (VF) during electrophysiological study...
2016: PloS One
Susana Cañón, Ricardo Caballero, Adela Herraiz-Martínez, Marta Pérez-Hernández, Begoña López, Felipe Atienza, José Jalife, Leif Hove-Madsen, Eva Delpón, Antonio Bernad
microRNAs (miR) have considerable potential as therapeutic tools in cardiac diseases. Alterations in atrial miR are involved in the development of atrial fibrillation (AF), but the molecular mechanism underlying their contribution to atrial remodeling in chronic atrial fibrillation (CAF) is only partially understood. Here we used miR array to analyze the miR profile of atrial biopsies from sinus rhythm (SR) and CAF patients. qRT-PCR identified a distinctive CAF-miR signature and described conserved miR-208b upregulation in human and ovine AF atrial tissue...
August 18, 2016: Journal of Molecular and Cellular Cardiology
Qing-Hua Guo, Bao-An Wang, Chen-Zhi Wang, Min Wang, Ju-Ming Lu, Zhao-Hui Lv, Yi-Ming Mu
BACKGROUND: Thyroid hormone resistance syndrome (THRS) is a rare disorder with increased concentrations of free thyroxine (FT4) and triiodothyronine (FT3), but normal or slightly increased thyroid-stimulating hormone (TSH). The mutations in the thyroid hormone receptor β (THRβ) gene are thought to be the main pathogenesis. OBJECTIVES: The aims of this study were to present 1 pedigree of Chinese THRS, summarize their clinical characteristics, and analyze the gene mutation...
August 2016: Medicine (Baltimore)
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