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Atrial Fibrillation Genes

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https://www.readbyqxmd.com/read/28429502/involvement-of-erk1-2-in-cx43-depression-induced-by-macrophage-migration-inhibitory-factor-in-atrial-myocytes
#1
Xin Li, Fang Rao, Chun-Yu Deng, Wei Wei, Fang-Zhou Liu, Hui Yang, Zhao-Yu Wang, Su-Juan Kuang, Xiao-Yan Chen, Yu-Mei Xue, Shu-Lin Wu
Connexin 43 (Cx43) plays an important role in the pathogenesis of atrial fibrillation (AF). The present study sought to investigate the effect of macrophage migration inhibitory factor (MIF), a pleiotropic cytokine, on Cx43 expression and activity and determine the intracellular signaling pathways. Cx43 protein and mRNA levels were assayed using immunofluorescence, real-time PCR, and western blot. We found that increased MIF and extracellular regulated protein kinases (ERK) expression was accompanied by a significant reduction in Cx43 protein expression in atrial tissues from patients with AF compared with those with sinus rhythm...
April 21, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28427903/atrial-fibrillation-is-associated-with-hypermethylation-in-human-left-atrium-and-treatment-with-decitabine-reduces-atrial-tachyarrhythmias-in-spontaneously-hypertensive-rats
#2
R Doñate Puertas, E Meugnier, C Romestaing, C Rey, E Morel, J Lachuer, N Gadot, A Scridon, C Julien, F Tronc, B Chapuis, C Valla, A Janin, L Pirola, A Méjat, S Rome, P Chevalier
Atrial fibrillation (AF) is the most common cardiac arrhythmia. As the molecular mechanisms underlying the pathology are largely unknown, this cardiac arrhythmia remains difficult to treat. To identify specific molecular actors involved in AF, we have performed a transcriptomic analysis on left atrium (LA) from patients with valvular heart disease with or without AF. We showed that 1627 genes had altered basal expression level in LA tissue of AF patients compared with the control group. The significantly enriched gene ontology biological process "anatomical structure morphogenesis" contained the highest number of genes in line with changes in structure that occur when the human heart remodels following AF development (ie, LA dilatation and interstitial fibrosis)...
March 30, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28427851/circulating-ceruloplasmin-ceruloplasmin-associated-genes-and-the-incidence-of-atrial-fibrillation-in-the-atherosclerosis-risk-in-communities-study
#3
Antonio P Arenas de Larriva, Faye L Norby, Lin Y Chen, Elsayed Z Soliman, Ron C Hoogeveen, Dan E Arking, Laura R Loehr, Alvaro Alonso
BACKGROUND: Ceruloplasmin (CP) may promote structural changes in the atrium making it more arrhythmogenic. We assessed the associations between CP, CP-associated genetic variants, and incident atrial fibrillation (AF) in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS: We studied 10,059 men and women without prevalent AF aged 53 to 75years in 1996-1998 and followed through 2012. Circulating CP was measured in stored blood samples obtained in 1996-1998...
April 6, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28427583/improving-atrial-fibrillation-therapy-is-there-a-gene-for-that
#4
REVIEW
William J Hucker, Alan Hanley, Patrick T Ellinor
Atrial fibrillation (AF) is an all-too-common and often challenging reality of clinical care. AF leads to significant morbidity and mortality; however, currently available treatments for AF have modest efficacy and high recurrence rates. In recent years, genetic therapy approaches have been explored in preclinical models of AF, and offer potential as a treatment modality with targeted delivery, tissue specificity, and therapy tailored to address mechanisms underlying the arrhythmia. However, many challenges remain before gene therapy can advance to a clinically relevant AF treatment...
April 25, 2017: Journal of the American College of Cardiology
https://www.readbyqxmd.com/read/28418895/gender-differences-in-fibrosis-remodeling-in-patients-with-long-standing-persistent-atrial-fibrillation
#5
Zhi Li, Zengwei Wang, Zongtao Yin, Yuji Zhang, Xiaodong Xue, Jinsong Han, Yan Zhu, Jian Zhang, Maximilian Y Emmert, Huishan Wang
The success rate of catheter ablation in atrial fibrillation (AF) is known to be lower in females than in males. However, while the exact mechanism for this phenomenon remains to be elucidated, tissue fibrosis may play an important role in this regard. It has been shown that fibrosis promotes AF and its recurrence, thereby substantially reducing the efficacy of catheter ablation in AF patients. Thus, we hypothesized that fibrosis may contribute to gender differences in the outcomes of AF catheter ablation.Here we systematically assessed pulmonary vein sleeves obtained from 166 patients with and without long-standing persistent-AF (LSP-AF) in order to identify gender-specific mechanistic differences in fibrosis remodeling of AF patients...
March 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416822/identification-of-six-new-genetic-loci-associated-with-atrial-fibrillation-in-the-japanese-population
#6
Siew-Kee Low, Atsushi Takahashi, Yusuke Ebana, Kouichi Ozaki, Ingrid E Christophersen, Patrick T Ellinor, Soichi Ogishima, Masayuki Yamamoto, Mamoru Satoh, Makoto Sasaki, Taiki Yamaji, Motoki Iwasaki, Shoichiro Tsugane, Keitaro Tanaka, Mariko Naito, Kenji Wakai, Hideo Tanaka, Tetsushi Furukawa, Michiaki Kubo, Kaoru Ito, Yoichiro Kamatani, Toshihiro Tanaka
Atrial fibrillation is the most common cardiac arrhythmia and leads to stroke. To investigate genetic loci associated with atrial fibrillation in the Japanese population, we performed a genome-wide association study (GWAS) that included 8,180 atrial fibrillation cases and 28,612 controls with follow-up in an additional 3,120 cases and 125,064 controls. We replicated previously reported loci and identified six new loci, near the KCND3, PPFIA4, SLC1A4-CEP68, HAND2, NEBL and SH3PXD2A genes. Five of the six new loci were specifically associated with atrial fibrillation in the Japanese population after comparing our data to those from individuals of European ancestry, suggesting that there might be different genetic factors affecting susceptibility across ancestry groups...
April 17, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28416818/large-scale-analyses-of-common-and-rare-variants-identify-12-new-loci-associated-with-atrial-fibrillation
#7
(no author information available yet)
Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents...
April 17, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28392310/the-role-of-the-autonomic-nervous-system-in-arrhythmias-and-sudden-cardiac-death
#8
REVIEW
Sonia Franciosi, Frances K G Perry, Thomas M Roston, Kathryn R Armstrong, Victoria E Claydon, Shubhayan Sanatani
The autonomic nervous system (ANS) is complex and plays an important role in cardiac arrhythmia pathogenesis. A deeper understanding of the anatomy and development of the ANS has shed light on its involvement in cardiac arrhythmias. Alterations in levels of Sema-3a and NGF, both growth factors involved in innervation patterning during development of the ANS, leads to cardiac arrhythmias. Dysregulation of the ANS, including polymorphisms in genes involved in ANS development, have been implicated in sudden infant death syndrome...
March 31, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28381466/intracellular-angiotensin-ii-interacts-with-nuclear-angiotensin-receptors-in-cardiac-fibroblasts-and-regulates-rna-synthesis-cell-proliferation-and-collagen-secretion
#9
Artavazd Tadevosyan, Jiening Xiao, Sirirat Surinkaew, Patrice Naud, Clémence Merlen, Masahide Harada, Xiaoyan Qi, David Chatenet, Alain Fournier, Bruce G Allen, Stanley Nattel
BACKGROUND: Cardiac fibroblasts play important functional and pathophysiological roles. Intracellular ("intracrine") angiotensin-II (Ang-II) signaling regulates intercellular communication, excitability, and gene expression in cardiomyocytes; however, the existence and role of intracrine Ang-II signaling in cardiac fibroblasts is unstudied. Here, we evaluated the localization of Ang-II receptors on atrial fibroblast nuclei and associated intracrine effects of potential functional significance...
April 5, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28381281/association-of-atrial-fibrillation-susceptibility-genes-atrial-fibrillation-phenotypes-and-response-to-catheter-ablation-a-gene-based-analysis-of-gwas-data
#10
Daniela Husser, Petra Büttner, Laura Ueberham, Borislav Dinov, Philipp Sommer, Arash Arya, Gerhard Hindricks, Andreas Bollmann
BACKGROUND: Previous studies have suggested PITX2, KCNN3 and ZFHX3 as atrial fibrillation (AF) susceptibility genes. Single common genetic polymorphisms of those genes have been linked with AF phenotypes and rhythm outcome of AF catheter ablation although their mechanisms remain elusive. New gene-based association tests may help clarifying genotype-phenotype correlations. Therefore, we hypothesized that PITX2, KCNN3 and ZFHX3 associate with left atrial enlargement and persistent AF and subsequently with ablation outcome...
April 5, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28337273/t-box-family-of-transcription-factor-tbx5-insights-in-development-and-disease
#11
Ting Zhu, Longwei Qiao, Qian Wang, Rui Mi, Jinnan Chen, Yaojuan Lu, Junxia Gu, Qiping Zheng
The T-box gene family refers to a group of transcription factors that share a highly conserved, sequence-specific DNA-binding domain (T-box) containing around 180-amino acids. According to HUGO gene nomenclature committee (HGNC), there are 18 T-box family members. These T-box genes have been implicated essential roles during embryogenesis and cardiac development, given their specific expression pattern in developing mammalian heart for several T-box genes, including TBX5. TBX5 is consisted of three transcriptional variants which cover 9 exons and encode two distinct isoforms that differ in N-terminus...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28306170/impact-of-atrial-fibrillation-on-platelet-gene-expression
#12
Waldemar E Wysokinski, Alfonso Tafur, Naser Ammash, Samuel J Asirvatham, Yanhong Wu, Izabella Gosk-Bierska, Diane E Grill, Joshua P Slusser, Jozef Mruk, Robert D McBane
AIMS: Platelets retain cytoplasmic messenger RNA and are capable of protein biosynthesis. Several diseases are known to impact the platelet transcriptome but the effect of non-valvular atrial fibrillation (NVAF) on platelet RNA transcript is essentially unknown. The aim of this study was to evaluate the impact of NVAF on platelet RNA transcript by measuring platelet genes expression in consecutive NVAF patients before and 3-4 months after pulmonary vein isolation (PVI) and compared to normal sinus rhythm controls (NSR)...
March 17, 2017: European Journal of Haematology
https://www.readbyqxmd.com/read/28275069/atrial-arrhythmias-and-electroanatomical-remodeling-in-patients-with-left-ventricular-assist-devices
#13
Amrish Deshmukh, Gene Kim, Martin Burke, Emeka Anyanwu, Valluvan Jeevanandam, Nir Uriel, Roderick Tung, Cevher Ozcan
BACKGROUND: The incidence, predictors, and impact of atrial arrhythmias along with left atrial structural changes in patients with left ventricular assist devices (LVADs) remain undetermined. METHODS AND RESULTS: All patients who underwent LVAD implantation from 2008 to 2015 at the University of Chicago Medical Center were included. Electronic medical records, electrocardiograms, echocardiograms, and cardiac electrical device interrogations were reviewed. The association of arrhythmias and clinical covariates with survival was evaluated by Kaplan-Meier and Cox proportional hazards analyses...
March 8, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28262340/gain-of-function-mutation-in-scn5a-causes-ventricular-arrhythmias-and-early-onset-atrial-fibrillation
#14
Krystien V Lieve, Arie O Verkerk, Svitlana Podliesna, Christian van der Werf, Michael W Tanck, Nynke Hofman, Paul F van Bergen, Leander Beekman, Connie R Bezzina, Arthur A M Wilde, Elisabeth M Lodder
BACKGROUND: Mutations in SCN5A, the gene encoding the α-subunit of the cardiac sodium channel (NaV1.5), are associated with a broad spectrum of inherited cardiac arrhythmia disorders. The purpose of this study was to identify the genetic and functional determinants underlying a Dutch family that presented with a combined phenotype of ventricular arrhythmias with a likely adrenergic component, either in isolation or in combination with a mildly decreased heart function and early onset (<55years) atrial fibrillation...
January 29, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/28256509/customized-laboratory-tlr4-and-tlr2-detection-method-from-peripheral-human-blood-for-early-detection-of-doxorubicin-induced-cardiotoxicity
#15
A L Pop-Moldovan, N-M Trofenciuc, D A Dărăbanţiu, C Precup, H Branea, R Christodorescu, M Puşchiţă
Cancer treatments can have significant cardiovascular adverse effects that can cause cardiomyopathy and heart failure with reduced survival benefit and considerable decrease in the use of antineoplastic therapy. The purpose of this study is to assess the role of TLR2 and TLR4 gene expression as an early marker for the risk of doxorubicin-induced cardiomyopathy in correlation with early diastolic dysfunction in patients treated with doxorubicin. Our study included 25 consecutive patients who received treatment with doxorubicin for hematological malignancies (leukemia, lymphomas or multiple myeloma), aged 18-65 years, with a survival probability>6 months and with left ventricular ejection fraction>50%...
March 3, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28239561/regulation-of-cardiac-cacnb2-by-microrna-499-potential-role-in-atrial-fibrillation
#16
Tian-You Ling, Xiao-Li Wang, Qiang Chai, Tong Lu, John M Stulak, Lyle D Joyce, Richard C Daly, Kevin L Greason, Li-Qun Wu, Win-Kuang Shen, Yong-Mei Cha, Hon-Chi Lee
The L-type calcium channel (LTCC) is one of the major ion channels that are known to be associated with the electrical remodeling of atrial fibrillation (AF). In AF, there is significant downregulation of the LTCC, but the underlying mechanism for such downregulation is not clear. We have previously reported that microRNA-499 (miR-499) is significantly upregulated in patients with permanent AF and that KCNN3, the gene that encodes the small-conductance calcium-activated potassium channel 3 (SK3), is a target of miR-499...
June 2017: BBA Clinical
https://www.readbyqxmd.com/read/28217939/pitx2-dependent-gene-regulation-in-atrial-fibrillation-and-rhythm-control
#17
Fahima Syeda, Paulus Kirchhof, Larissa Fabritz
Atrial fibrillation (AF) is a common arrhythmia. Better prevention and treatment of AF are needed to reduce AF-associated morbidity and mortality. There are several major mechanisms that cause AF in patients, including a genetic predisposition to develop AF. Genome-wide association studies (GWAS) have identified genetic variants associated with AF populations, with the strongest hits clustering on chromosome 4q25, close to the gene for the homeobox transcription factor PITX2. The effect of these common gene variants on cardiac PITX2 mRNA is currently under study...
February 19, 2017: Journal of Physiology
https://www.readbyqxmd.com/read/28208135/abcb1-and-slco1b3-gene-polymorphisms-and-their-impact-on-digoxin-pharmacokinetics-in-atrial-fibrillation-patients-among-the-tunisian-population
#18
Nejia Tounsi, Imen Trabelsi, Emna Kerkeni, Mohamed Habib Grissa, Nizar Fredj, Adel Sekma, Malek Mzali, Ilhem Hellara, Kamel Monastiri, Wahiba Douki, Semir Nouira
BACKGROUND: Digoxin is a substrate of P-glycoprotein (P-gp) and organic anion transporting polypeptide transporters that are encoded by ABCB1 and SLCO1B3 genes. Genetic polymorphisms in both genes may explain inter-individual variability of serum digoxin concentration (SDC). This study evaluates the possible effect of the most common ABCB1 and SLCO1B3 polymorphisms on SDC after a single oral dose of digoxin in Tunisian atrial fibrillation (AF) patients. METHODS: ABCB1 and SLCO1B3 genotypes were analyzed in 102 patients with AF who received digoxin (0...
2017: Pharmacology
https://www.readbyqxmd.com/read/28205526/association-evidence-of-ccttt-repeat-polymorphism-in-the-inos-promoter-and-the-risk-of-atrial-fibrillation-in-taiwanese
#19
Lung-An Hsu, Yung-Hsin Yeh, Wei-Jan Chen, Chi-Tai Kuo, Feng-Chun Tsai, Yi-Hsin Chan, Chun-Li Wang, Chi-Jen Chang, Hsin-Yi Tsai
Inducible nitric oxide synthase (iNOS) plays an important role in the pathogenesis of atrial fibrillation (AF). The iNOS promoter has a CCTTT-repeat length polymorphism that can determine the level of gene transcription. This study enrolled 200 AF patients and 240 controls. The length of CCTTT-repeat polymorphism in the iNOS promoter region was examined by polymerase chain reactions, with the alleles with ≤11 repeats designated as S and alleles with ≥12 repeats designated as L alleles. AF patients carried significantly higher frequencies of the LL genotype than control subjects (40...
February 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28169950/update-about-atrial-fibrillation-genetics
#20
Alexandra Pérez-Serra, Oscar Campuzano, Ramon Brugada
PURPOSE OF REVIEW: Atrial fibrillation is an important cause of morbidity in the aging population. The mechanisms responsible for the triggering and maintenance of the chaotic atrial rhythm are still poorly understood. In this review, we will focus on the genetic aspects of atrial fibrillation, to understand causality, with special emphasis on recent studies published in the field. RECENT FINDINGS: Diseases such as hypertension, valvular heart disease, and heart failure may induce atrial fibrillation, which increases the risk of stroke and sudden cardiac death...
February 4, 2017: Current Opinion in Cardiology
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