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CLC number: R542.2

On-line Access: 2019-08-05

Received: 2019-01-12

Revision Accepted: 2019-05-04

Crosschecked: 2019-07-09

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Journal of Zhejiang University SCIENCE B 2019 Vol.20 No.9 P.766-775

http://doi.org/10.1631/jzus.B1900017


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


Author(s):  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

Affiliation(s):  Department of Cardiology, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, China; more

Corresponding email(s):   gxg22222@zju.edu.cn

Key Words:  Idiopathic dilated cardiomyopathy, Implantable cardioverter defibrillator (ICD), LIM domain binding 3 (LDB3), Polymorphism, Han Chinese


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. Impact of LDB3 gene polymorphisms on clinical presentation and implantable cardioverter defibrillator (ICD) implantation in Chinese patients with idiopathic dilated cardiomyopathy[J]. Journal of Zhejiang University Science B, 2019, 20(9): 766-775.

@article{title="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, 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",
journal="Journal of Zhejiang University Science B",
volume="20",
number="9",
pages="766-775",
year="2019",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1900017"
}

%0 Journal Article
%T Impact of LDB3 gene polymorphisms on clinical presentation and implantable cardioverter defibrillator (ICD) implantation in Chinese patients with idiopathic dilated cardiomyopathy
%A Dong-Fei Wang
%A Jia-Lan Lyu
%A Juan Fang
%A Jian Chen
%A Wan-Wan Chen
%A Jia-Qi Huang
%A Shu-Dong Xia
%A Jian-Mei Jin
%A Fang-Hong Dong
%A Hong-Qiang Cheng
%A Ying-Ke Xu
%A Xiao-Gang Guo
%J Journal of Zhejiang University SCIENCE B
%V 20
%N 9
%P 766-775
%@ 1673-1581
%D 2019
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1900017

TY - JOUR
T1 - Impact of LDB3 gene polymorphisms on clinical presentation and implantable cardioverter defibrillator (ICD) implantation in Chinese patients with idiopathic dilated cardiomyopathy
A1 - Dong-Fei Wang
A1 - Jia-Lan Lyu
A1 - Juan Fang
A1 - Jian Chen
A1 - Wan-Wan Chen
A1 - Jia-Qi Huang
A1 - Shu-Dong Xia
A1 - Jian-Mei Jin
A1 - Fang-Hong Dong
A1 - Hong-Qiang Cheng
A1 - Ying-Ke Xu
A1 - Xiao-Gang Guo
J0 - Journal of Zhejiang University Science B
VL - 20
IS - 9
SP - 766
EP - 775
%@ 1673-1581
Y1 - 2019
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1900017


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.

中国汉族特发性扩张型心肌病患者LDB3基因多态性与临床表现及植入型心律转复除颤器(ICD)植入的相关性研究

目的:探讨LDB3(LIM domain binding 3)基因多态性与中国汉族特发性扩张型心肌病发病的相关性,并分析LDB3基因多态性对患者临床表现和植入型心律转复除颤器(ICD)植入的影响.
创新点:首次明确LDB3基因多态性与中国汉族特发性扩张型心肌病发病密切相关,发现了三个与脑钠肽、舒张压、左室射血分数相关的多态性位点和一个与植入心律转复除颤器相关的多态性位点.
方法:本研究纳入我院159例中国汉族特发性扩张型心肌病患者和247例无亲缘关系健康对照并收集基线临床资料.提取外周血DNA后,聚合酶链式反应扩增LDB3基因的14个外显子,经Sanger一代测序,获得基因突变位点.通过关联分析,研究基因多态性与特发性扩张型心肌病发病之间的相关性.根据连锁不平衡系数和基因分布频率进行单倍体分析,研究不同单倍体分型对特发性扩张型心肌病发病的影响.
结论:LDB3基因多态性分析中,发现9个多态性位点符合哈代-温伯格平衡.其中rs4468255位点多态性与中国汉族特发性扩张型心肌病发病密切相关.rs11812601、rs56165849和rs3740346位点多态性与患者舒张压、左室射血分数存在显著关联(P<0.05).且携带rs4468255多态性的患者更倾向于安装植入型心律转复除颤器.

关键词:特发性扩张型心肌病;植入型心律转复除颤器;LDB3;基因多态性;中国汉族

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[30]List of electronic supplementary materials

[31]Table S1 Primer sequences of LDB3 gene used in polymerase chain reaction

[32]Table S2 Hardy-Weinberg equilibrium (HWE) testing among cases and controls

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