Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease

Михайлов, А. И.; Torrado, Mario

doi:10.1007/s10741-016-9569-0

Cited by 12 publications

(16 citation statements)

References 140 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These structural defects often cause conduction diseases, such as arrhythmia and atrioventricular block [3,21,22]. In addition, TBX5 is considered to play a role in diastolic function, through Ca 2+ handling modulation [23][24][25]. TBX5 variants have been identified in patients https://doi.org/10.1371/journal.pone.0227393.g001…”

Section: Discussionmentioning

confidence: 99%

TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway

et al. 2020

View full text Add to dashboard Cite

Background TBX5 is a transcription factor that has an important role in development of heart. TBX5 variants in the region encoding the T-box domain have been shown to cause cardiac defects, such as atrial septal defect or ventricular septal defect, while TBX5 variants have also been identified in a few cardiomyopathy patients and considered causative. We identified a TBX5 variant (c.791G>A, p.Arg264Lys), that is over-represented in cardiomyopathy patients. This variant is located outside of the T-box domain, and its pathogenicity has not been confirmed by functional analyses. Objective To investigate whether the TBX5 R264K is deleterious and could contribute to the pathogenesis of cardiomyopathy. Methods and results We developed mice expressing Tbx5 R264K. Mice homozygous for this variant displayed compensated dilated cardiomyopathy; mild decreased fractional shortening, dilatation of the left ventricle, left ventricular wall thinning and increased heart weight without major heart structural disorders. There was no difference in activation of the ANF promotor, a transcriptional target of Tbx5, compared to wild-type. However, analysis of RNA isolated from left ventricular samples showed significant increases in the expression of Acta1 in left ventricle with concomitant increases in the protein level of ACTA1.

show abstract

Section: Discussionmentioning

confidence: 99%

TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway

et al. 2020

View full text Add to dashboard Cite

show abstract

“…MYOCD codes for a nuclear protein (myocardin) expressed in cardiomyocytes and smooth muscle cell-containing tissues. MYOCD has been shown to be essential for maintaining adult heart function (24). Mice in which The second novel locus found in this study involved an intronic SNP in SYT1.…”

Section: Discussionmentioning

confidence: 64%

GWAS of QRS Duration Identifies New Loci Specific to Hispanic/Latino Populations Swenson Hispanic/Latino QRS GWAS

Swenson

Louie

Lin

et al. 2018

Preprint

View full text Add to dashboard Cite

words Text 4160 words Journal Subject Terms:Genetic, Association Studies; ECG; Epidemiology; Race and Ethnicity All rights reserved. No reuse allowed without permission.was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint (which . http://dx.doi.org/10.1101/363457 doi: bioRxiv preprint first posted online Jul. 6, 2018; 4 ABSTRACT Background. The electrocardiographically quantified QRS duration measures

show abstract

“…MYOCD has been shown to be essential for maintaining adult heart function. [27] Mice in which MYOCD is postnatally knocked down develop dilated cardiomyopathy and fatal heart failure. [28] A genetic study of Dominican families found evidence that MYOCD was associated with left atrial size.…”

Section: Discussionmentioning

confidence: 99%

GWAS of QRS duration identifies new loci specific to Hispanic/Latino populations

et al. 2019

View full text Add to dashboard Cite

Background The electrocardiographically quantified QRS duration measures ventricular depolarization and conduction. QRS prolongation has been associated with poor heart failure prognosis and cardiovascular mortality, including sudden death. While previous genome-wide association studies (GWAS) have identified 32 QRS SNPs across 26 loci among European, African, and Asian-descent populations, the genetics of QRS among Hispanics/Latinos has not been previously explored. Methods We performed a GWAS of QRS duration among Hispanic/Latino ancestry populations (n = 15,124) from four studies using 1000 Genomes imputed genotype data (adjusted for age, sex, global ancestry, clinical and study-specific covariates). Study-specific results were combined using fixed-effects, inverse variance-weighted meta-analysis. Results We identified six loci associated with QRS ( P <5x10 -8 ), including two novel loci: MYOCD , a nuclear protein expressed in the heart, and SYT1 , an integral membrane protein. The top SNP in the MYOCD locus, intronic SNP rs16946539, was found in Hispanics/Latinos with a minor allele frequency (MAF) of 0.04, but is monomorphic in European and African descent populations. The most significant QRS duration association was with intronic SNP rs3922344 ( P = 1.19x10 -24 ) in SCN5A/SCN10A . Three other previously identified loci, CDKN1A , VTI1A , and HAND1 , also exceeded the GWAS significance threshold among Hispanics/Latinos. A total of 27 of 32 previously identified QRS duration SNPs were shown to generalize in Hispanics/Latinos. Conclusions Our QRS duration GWAS, the first in Hispanic/Latino populations, identified two new loci, underscoring the utility of extending large scale genomic studies to currently under-examined populations.

show abstract

Myocardial transcription factors in diastolic dysfunction: clues for model systems and disease

Cited by 12 publications

References 140 publications

TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway

TBX5 R264K acts as a modifier to develop dilated cardiomyopathy in mice independently of T-box pathway

GWAS of QRS Duration Identifies New Loci Specific to Hispanic/Latino Populations Swenson Hispanic/Latino QRS GWAS

GWAS of QRS duration identifies new loci specific to Hispanic/Latino populations

Contact Info

Product

Resources

About