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

doi:10.1631/jzus.B1900017

. 2019;20(9):766-775.

doi: 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

Affiliations

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.

PMID: 31379146
PMCID: PMC6700353
DOI: 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

Dong-Fei Wang et al. J Zhejiang Univ Sci B. 2019.

. 2019;20(9):766-775.

doi: 10.1631/jzus.B1900017.

Authors

Affiliations

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.

PMID: 31379146
PMCID: PMC6700353
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.

Keywords: Idiopathic dilated cardiomyopathy; Implantable cardioverter defibrillator (ICD); LIM domain binding 3 (LDB3); Polymorphism; Han Chinese.

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Conflict of interest statement

Compliance with ethics guidelines: 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, and Xiao-gang GUO declare that they have no conflict of interest.

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2008 (5). Informed consent was obtained from all patients for being included in the study.

Figures

**Fig. 1**
Pairwise SNP linkage disequilibrium map The D' values are shown inside each diamond. The map was drawn based on the genotype data of all case and control samples using SHEsis

See this image and copyright information in PMC

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References

1. Bänsch D, Antz M, Boczor S, et al. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the cardiomyopathy trial (CAT) Circulation. 2002;105(12):1453–1458. doi: 10.1161/01.CIR.0000012350.99718.AD. - DOI - PubMed
1. Bondue A, Arbustini E, Bianco A, et al. Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial function of the European Society of Cardiology. Cardiovasc Res. 2018;114(10):1287–1303. doi: 10.1093/cvr/cvy122. - DOI - PMC - PubMed
1. Faulkner G, Pallavicini A, Formentin E, et al. ZASP: a new Z-band alternatively spliced PDZ-motif protein. J Cell Biol. 1999;146(2):465–475. doi: 10.1083/jcb.146.2.465. - DOI - PMC - PubMed
1. Garfinkel AC, Seidman JG, Seidman CE. Genetic pathogenesis of hypertrophic and dilated cardiomyopathy. Heart Fail Clin. 2018;14(2):139–146. doi: 10.1016/j.hfc.2017.12.004. - DOI - PMC - PubMed
1. Glöcklhofer CR, Steinfurt J, Franke G, et al. A novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy with high risk of sudden cardiac death in a large five-generation family. EP Europace. 2018;20(12):2003–2013. doi: 10.1093/europace/euy127. - DOI - PubMed

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[1] Bänsch D, Antz M, Boczor S, et al. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the cardiomyopathy trial (CAT) Circulation. 2002;105(12):1453–1458. doi: 10.1161/01.CIR.0000012350.99718.AD. - DOI - PubMed

[2] Bänsch D, Antz M, Boczor S, et al. Primary prevention of sudden cardiac death in idiopathic dilated cardiomyopathy: the cardiomyopathy trial (CAT) Circulation. 2002;105(12):1453–1458. doi: 10.1161/01.CIR.0000012350.99718.AD. - DOI - PubMed

[3] Bondue A, Arbustini E, Bianco A, et al. Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial function of the European Society of Cardiology. Cardiovasc Res. 2018;114(10):1287–1303. doi: 10.1093/cvr/cvy122. - DOI - PMC - PubMed

[4] Bondue A, Arbustini E, Bianco A, et al. Complex roads from genotype to phenotype in dilated cardiomyopathy: scientific update from the Working Group of Myocardial function of the European Society of Cardiology. Cardiovasc Res. 2018;114(10):1287–1303. doi: 10.1093/cvr/cvy122. - DOI - PMC - PubMed

[5] Faulkner G, Pallavicini A, Formentin E, et al. ZASP: a new Z-band alternatively spliced PDZ-motif protein. J Cell Biol. 1999;146(2):465–475. doi: 10.1083/jcb.146.2.465. - DOI - PMC - PubMed

[6] Faulkner G, Pallavicini A, Formentin E, et al. ZASP: a new Z-band alternatively spliced PDZ-motif protein. J Cell Biol. 1999;146(2):465–475. doi: 10.1083/jcb.146.2.465. - DOI - PMC - PubMed

[7] Garfinkel AC, Seidman JG, Seidman CE. Genetic pathogenesis of hypertrophic and dilated cardiomyopathy. Heart Fail Clin. 2018;14(2):139–146. doi: 10.1016/j.hfc.2017.12.004. - DOI - PMC - PubMed

[8] Garfinkel AC, Seidman JG, Seidman CE. Genetic pathogenesis of hypertrophic and dilated cardiomyopathy. Heart Fail Clin. 2018;14(2):139–146. doi: 10.1016/j.hfc.2017.12.004. - DOI - PMC - PubMed

[9] Glöcklhofer CR, Steinfurt J, Franke G, et al. A novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy with high risk of sudden cardiac death in a large five-generation family. EP Europace. 2018;20(12):2003–2013. doi: 10.1093/europace/euy127. - DOI - PubMed

[10] Glöcklhofer CR, Steinfurt J, Franke G, et al. A novel LMNA nonsense mutation causes two distinct phenotypes of cardiomyopathy with high risk of sudden cardiac death in a large five-generation family. EP Europace. 2018;20(12):2003–2013. doi: 10.1093/europace/euy127. - DOI - PubMed

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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

Affiliations

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

Authors

Affiliations

Abstract

Conflict of interest statement

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