Impact of LDB3 gene polymorphisms on clinical presentation and implantable cardioverter defibrillator (ICD) implantation in Chinese patients with idiopathic dilated cardiomyopathy

Abstract

Objective: Mutations in LIM domain binding 3 (LDB3) gene cause idiopathic dilated cardiomyopathy (IDCM), a structural heart disease with a complicated genetic background. However, the association of polymorphisms in the LDB3 gene with susceptibility to IDCM in Chinese populations remains unexplored as dose the impact on clinical presentation. Methods: We sequenced all exons and the adjacent part of introns of the LDB3 gene in 159 Chinese Han IDCM patients and 247 healthy controls. Then we detected the distribution of polymorphisms in the LDB3 gene in all participants and assessed their associations with risk of IDCM. Additionally, we conducted a stratified genotypephenotype correlation analysis. Results: The A allele of rs4468255 was significantly associated with IDCM (P<0.01). The rs4468255, rs11812601, rs56165849, and rs3740346 were also associated with diastolic blood pressure (DBP) and left ventricular ejection fraction (LVEF) (P<0.05). Notably, a higher frequency of rs4468255 polymorphism was observed in implantable cardioverter defibrillator (ICD) recipients under a recessive model (P<0.01), whereas the significant association disappeared after adjusting for potential confounders. However, in the dominant model, notable correlations could only be observed after adjusting for multi parameters. Conclusions: The rs4468255 was significantly correlated with IDCM of Chinese Han population. A allele of rs4468255 is higher in IDCM patients with ICD implantation, suggesting the influence of genetic background in the generation of this response. In addition, rs11812601, rs56165849, and rs3740346 in LDB3 show association with brain natriuretic peptide, DBP, and LVEF levels in patients with IDCM but did not show any association with IDCM susceptibility.

Transcriptome Profiling across Five Tissues of Giant Panda

“…CAV3 may act as a scaffolding protein within caveolar membranes, interacting directly with G-protein alpha subunits and can functionally regulate their activity (https://www.uniprot.org/), which can regulate caveolae function [62]. LDB3 gene mutations cause idiopathic dilated cardiomyopathy (IDCM) [63] and sometimes occur simultaneously with both prominent left ventricular trabeculation and congenital left ventricular aneurysms [64]. TRDN contributes to the regulation of lumenal Ca2+ release via the sarcoplasmic reticulum calcium release channels RYR1 and RYR2, a key step in triggering skeletal and heart muscle contraction, and TRDN play a role in excitation-contraction coupling in the heart and in regulating the rate of heartbeats (https://www.uniprot.org/).…”

Anomalous right coronary artery originating from the aorta: a series of nine pediatric cases

“…The known diseases caused by mutations in the RYR2 gene are catecholamine-sensitive polymorphic ventricular tachycardia and arrhythmogenic right ventricular cardiomyopathy [ 33 ]. The known disease caused by mutations in the LDB3 gene is dilated cardiomyopathy [ 34 ]. One child was found to have a mutation in the GDF1 gene, and the known diseases caused by this mutation are right atrial heterogeneity and dextral aortic ectopia [ 35 ].…”

Actin-Binding Proteins in Cardiac Hypertrophy

“…Its interaction with the transcription factor may lead to cardiac hypertrophy, but the molecular mechanism of its mediating cardiac hypertrophy remains elusive. In addition, several LIM family proteins such as muscle LIM protein (MLP) and LIM domain-binding 3 have also been reported to play important roles in cardiac hypertrophy [ 93 , 94 ].…”