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

Dong-fei Wang; Jia-lan Lyu; Juan Fang; Jian Chen; Wan-wan Chen; Jia-qi Huang; Shu-dong Xia; Jian-mei Jin; Fang-hong Dong; Hong-qiang Cheng; Ying-ke XU; Xiao-gang Guo

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

Author: Dong-Fei WANG ¹ ; Jia-Lan LYU ¹ ; Juan FANG ¹ ; Jian CHEN ² ; Wan-Wan CHEN ³ ; Jia-Qi HUANG ⁴ ; Shu-Dong XIA ⁵ ; Jian-Mei JIN ¹ ; Fang-Hong DONG ¹ ; Hong-Qiang CHENG ⁴ ; Ying-Ke XU ⁶ ; Xiao-Gang GUO ¹
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1. Department of Cardiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China.
2. Department of Cardiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
3. Department of Cardiology, Pujiang Branch of the First Affiliated Hospital, School of Medicine, Zhejiang University, Jinhua 322200, China.
4. Department of Pathology and Pathophysiology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
5. Department of Cardiology, the Forth Affiliated Hospital, School of Medicine, Zhejiang University, Yiwu 322000, China.
6. Key Laboratory of Biomedical Engineering of Ministry of Education, Department of Biomedical Engineering, Zhejiang University, Hangzhou 310027, China.
Publication Type:Journal Article
Keywords: Idiopathic dilated cardiomyopathy; Implantable cardioverter defibrillator (ICD); LIM domain binding 3 (LDB3); Polymorphism; Han Chinese
MeSH: Adaptor Proteins, Signal Transducing/genetics*; Adult; Aged; Alleles; Asian People; Cardiomyopathy, Dilated/surgery*; China/epidemiology*; Defibrillators, Implantable; Exons; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genotype; Humans; LIM Domain Proteins/genetics*; Linkage Disequilibrium; Male; Middle Aged; Mutation; Polymorphism, Genetic; Sequence Analysis, DNA
From: Journal of Zhejiang University. Science. B 2019;20(9):766-775
CountryChina
Language:English
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 genotype-phenotype 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.