Calcium Signaling Pathway Genes RUNX2 and CACNA1C Are Associated With Calcific Aortic Valve Disease

Circulation. Cardiovascular Genetics
Sandra Guauque-OlarteYohan Bossé

Abstract

Calcific aortic valve stenosis (AS) is a life-threatening disease with no medical therapy. The genetic architecture of AS remains elusive. This study combines genome-wide association studies, gene expression, and expression quantitative trait loci mapping in human valve tissues to identify susceptibility genes of AS. A meta-analysis was performed combining the results of 2 genome-wide association studies in 474 and 486 cases from Quebec City (Canada) and Paris (France), respectively. Corresponding controls consisted of 2988 and 1864 individuals with European ancestry from the database of genotypes and phenotypes. mRNA expression levels were evaluated in 9 calcified and 8 normal aortic valves by RNA sequencing. The results were integrated with valve expression quantitative trait loci data obtained from 22 AS patients. Twenty-five single-nucleotide polymorphisms had P<5×10(-6) in the genome-wide association studies meta-analysis. The calcium signaling pathway was the top gene set enriched for genes mapped to moderately AS-associated single-nucleotide polymorphisms. Genes in this pathway were found differentially expressed in valves with and without AS. Two single-nucleotide polymorphisms located in RUNX2 (runt-related transcripti...Continue Reading

References

Jan 10, 1998·Pathology·B A Warren, J L Yong
Mar 19, 2003·Lancet·Helen M ColhounGeorge Davey Smith
Oct 6, 2004·Genome Biology·Robert C GentlemanJianhua Zhang
Nov 3, 2004·Journal of the American College of Cardiology·Satu HelskePetri T Kovanen
Nov 3, 2004·Circulation·Benjamin D HorneLisa A Cannon-Albright
Jun 10, 2005·The New England Journal of Medicine·S Joanna CowellScottish Aortic Stenosis and Lipid Lowering Trial, Impact on Regression (SALTIRE) Investigators
Jul 19, 2005·Nature·Vidu GargDeepak Srivastava
Feb 8, 2006·Circulation·Vincent ProbstJean-Jacques Schott
Sep 19, 2006·Lancet·Vuyisile T NkomoMaurice Enriquez-Sarano
Dec 30, 2006·PLoS Genetics·Nick PattersonDavid Reich
Apr 26, 2007·Nature Clinical Practice. Cardiovascular Medicine·Nalini M RajamannanShahbudin H Rahimtoola
Sep 28, 2007·Nature Genetics·Matthew D MailmanStephen T Sherry
May 10, 2008·Bioinformatics·Pan DuSimon M Lin
Sep 4, 2008·The New England Journal of Medicine·Anne B RossebøSEAS Investigators
Feb 24, 2009·Lancet·Blase A Carabello, Walter J Paulus
Aug 1, 2009·Science·Antigone S DimasStylianos E Antonarakis
May 27, 2010·Nucleic Acids Research·Dougu NamSangsoo Kim
Jul 17, 2010·Bioinformatics·Randall J PruimCristen J Willer
Oct 29, 2010·Genome Biology·Simon Anders, Wolfgang Huber
Mar 30, 2011·Hypertension·Andrew D JohnsonWomen's Genome Health Study
Aug 23, 2011·The American Journal of Cardiology·Nathalie GaudreaultYohan Bossé
Dec 6, 2011·Nature Methods·Olivier DelaneauJean-François Zagury
Jan 19, 2012·International Journal of Epidemiology·Orestis A PanagiotouGenome-Wide Significance Project
Dec 12, 2012·Nature Biotechnology·Cole TrapnellLior Pachter
Feb 8, 2013·The New England Journal of Medicine·George ThanassoulisCHARGE Extracoronary Calcium Working Group
Mar 5, 2013·International Journal of Cardiology·Edit NagyMagnus Bäck
Jul 9, 2013·Circulation Research·Dwight A Towler
Jul 10, 2013·Nature Reviews. Genetics·Teri A Manolio
Mar 19, 2014·Journal of Molecular and Cellular Cardiology·Diala El HusseiniPatrick Mathieu
Dec 19, 2014·Circulation·Dariush MozaffarianAmerican Heart Association Statistics Committee and Stroke Statistics Subcommittee

Citations

May 5, 2016·Neuroscience·Katerina Zorina-LichtenwalterL Diatchenko
May 5, 2017·Clinical Medicine Insights. Cardiology·Thomas M RostonShubhayan Sanatani
Nov 11, 2017·Disease Models & Mechanisms·Xin GengR Sathish Srinivasan
Nov 30, 2016·Circulation·Guillaume Marquis-GravelPhilippe Généreux
Dec 16, 2017·Circulation. Cardiovascular Genetics·Andreas MartinssonJ Gustav Smith
Mar 8, 2018·Nature Communications·Anna HelgadottirKari Stefansson
May 18, 2016·Nature Reviews. Disease Primers·Brian R LindmanPhilippe Pibarot
Sep 6, 2020·Current Opinion in Rheumatology·Sofia Serena Tsakali, Catherine M Shanahan
Jul 16, 2020·International Journal of Molecular Sciences·Gaia PedrialiPaolo Pinton
Dec 12, 2018·Nature Reviews. Cardiology·Maximillian A Rogers, Elena Aikawa
Dec 21, 2019·BMC Cardiovascular Disorders·Jonna WeisellJaana Rysä
Aug 18, 2017·Expert Review of Cardiovascular Therapy·Patrick MathieuMarlys L Koschinsky
Jan 6, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yongjiang QianZhongqun Wang
Oct 28, 2020·Annual Review of Physiology·Geoffrey S PittChike Cao
Feb 4, 2021·JACC. Basic to Translational Science·Rihab BoucharebDjamel Lebeche
Apr 30, 2021·Circulation Research·Mark C BlaserElena Aikawa
Apr 21, 2021·Cardiovascular Research·Harry Z E GreenbergMin Zhang

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Spatio-Temporal Regulation of DNA Repair

DNA repair is a complex process regulated by several different classes of enzymes, including ligases, endonucleases, and polymerases. This feed focuses on the spatial and temporal regulation that accompanies DNA damage signaling and repair enzymes and processes.

Glut1 Deficiency

Glut1 deficiency, an autosomal dominant, genetic metabolic disorder associated with a deficiency of GLUT1, the protein that transports glucose across the blood brain barrier, is characterized by mental and motor developmental delays and infantile seizures. Follow the latest research on Glut1 deficiency with this feed.

Hereditary Sensory Autonomic Neuropathy

Hereditary Sensory Autonomic Neuropathies are a group of inherited neurodegenerative disorders characterized clinically by loss of sensation and autonomic dysfunction. Here is the latest research on these neuropathies.

Separation Anxiety

Separation anxiety is a type of anxiety disorder that involves excessive distress and anxiety with separation. This may include separation from places or people to which they have a strong emotional connection with. It often affects children more than adults. Here is the latest research on separation anxiety.

Neural Activity: Imaging

Imaging of neural activity in vivo has developed rapidly recently with the advancement of fluorescence microscopy, including new applications using miniaturized microscopes (miniscopes). This feed follows the progress in this growing field.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.