Novel GATA4 mutations in lone atrial fibrillation

Jiang, Jianfei; Shen, Fangfang; Fang, Wei-Yi; Liu, Xu; Yang, Yi‐Qing

doi:10.3892/ijmm.2011.783

Cited by 27 publications

(11 citation statements)

References 54 publications

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“…A growing body of evidence indicates that genetic factors are significant in the pathogenesis of lone AF and familial AF (2–4), with our previous studies indicating a genetic predisposition in familial AF (2,5). However, the mechanism underlying this disorder remains unclear.…”

Section: Introductionsupporting

confidence: 50%

Association of angiotensin-converting enzyme gene I/D and CYP11B2 gene −344T/C polymorphisms with lone atrial fibrillation and its recurrence after catheter ablation

Zhang¹,

Wu²,

Liu³

et al. 2012

Experimental and Therapeutic Medicine

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The renin-angiotensin-aldosterone system (RAAS) plays a key role in atrial structural and electrical remodeling. The aim of this study was to investigate the potential associations of angiotensin-converting enzyme (ACE) gene insertion/ deletion (I/D) and aldosterone synthase (CYP11B2) gene −344T/C polymorphisms with the risk and recurrence of lone atrial fibrillation (AF). One hundred and ninety-three patients who underwent successful catheter ablation for lone AF were recruited. Two hundred and ninety-seven sinus rhythm subjects without a history of arrhythmia served as controls. The subjects were genotyped for ACE gene I/D and CYP11B2 gene −344T/C polymorphisms. Results showed that the ACE gene DD genotype and D allele were associated with a greater prevalence of lone AF (both P<0.01). In addition, the ACE gene DD genotype had a significantly larger left atrial dimension (LAD; 41.6±5.7 mm vs. 39.6±5.2 mm; P=0.043) and higher risk of AF recurrence [44.7% vs. 23.2%; odds ratio (OR), 2.68; 95% confidence interval (CI), 1.28–5.61; P=0.008] compared with the II+ID genotype in lone AF patients. After adjustment for a variety of risk factors, the ACE gene DD genotype had a 1.97-fold increased risk for lone AF (OR, 1.97; 95% CI, 1.15–3.37; P= 0.013) and 2.35-fold increased risk for AF recurrence (RR, 2.35; 95% CI, 1.10–5.04; P=0.028) compared with the ACE gene II+ID genotype. However, no correlation between the CYP11B2 gene −344T/C polymorphism and lone AF or its recurrence was observed in this cohort. In conclusion, the ACE gene DD genotype was associated with an increased incidence of lone AF and its recurrence following ablation, which was partly mediated by LAD.

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Section: Introductionsupporting

confidence: 50%

Association of angiotensin-converting enzyme gene I/D and CYP11B2 gene −344T/C polymorphisms with lone atrial fibrillation and its recurrence after catheter ablation

Zhang¹,

Wu²,

Liu³

et al. 2012

Experimental and Therapeutic Medicine

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“…Here we report 9 rare variants out of which 5 Table S3). Our study along with other existing reports suggest that the frequency of GATA4 mutations is more in N-terminal transactivation domain despite of the fact that zinc finger DNA-binding domain of GATA4 is critical for GATA4 function (Butler et al, 2010;Jiang, Shen, Fang, Liu, & Yang, 2011;Tomita-Mitchell et al, 2007;Yang & Gharibeh, et al, 2013;Yang & Li, et al, 2012;Zhang et al, 2008). Several of these studies have also demonstrated functional impairment of GATA4 caused due to mutations in this region Yang & Li, et al, 2012;Wang, Sun, & Yang, 2012;Yang & Gharibeh, et al, 2013).…”

Section: Discussionsupporting

confidence: 77%

Functionally significant, novelGATA4variants are frequently associated with Tetralogy of Fallot

Dixit

Narasimhan

Balekundri³

et al. 2018

Human Mutation

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Transcription factor GATA4 is known to play crucial role during heart development, regulating expression of several other key cardiogenic factors. Various GATA4 mutations are reported in familial as well as sporadic cases of congenital heart defects (CHDs). To estimate the prevalence and pathogenic potential of GATA4 variants in our CHD cohort, we have screened 285 CHD cases along with 200 controls by Sanger sequencing and identified 9 genetic variants (c.23C>A; p.Ala8Asp, c.25G>A; p.Ala9Thr, c.223G>T; p.Ala75Ser, c.383A>T; p.Glu128Val, c.397A>T; p.Ser133Cys, c.682T>A; p.Trp228Arg, c.1064C>G; p.Thr355Ser, c.1073G>C; p.Ser358Thr, and c.1220C>A; p.Pro407Gln) in 22 unrelated CHD probands (frequency:7.72%). Five of these are novel and located in the N-terminal transactivation domain (TAD) and first zinc finger domain. Majority C-terminal domain variants are polymorphic. Two of the TAD variants p.Glu128Val, p.Ser133Cys, and a first zinc finger variant p.Trp228Arg, impair combinatorial synergy of NKX2-5, SRF, and TBX5, suggesting potential role of these domains in GATA4 interactions with these factors. Decreased DNA-binding affinity with EMSA also supports this observation. Homology modeling and tertiary structure comparison show conformational changes in these variants. Interestingly, GATA4 variants are more frequently associated with ToF (45%; P = 0.0046) and PS (22.7%; P < 0.0001) in spite of abundance of septal defects in our study cohort.

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“…13–15 In addition, mutations in several transcription factors involved in atrial development have also been identified in patients with lone AF. 16–18 Yet the influence of these variants is complex: for instance in one example, two different alleles of the same SNP are associated with increased AF risk. 19, 20 Supplemental Table S1 provides a comprehensive list of AF associated rare variants or mutations that have been reported to date.…”

Section: The Role Of Rare Genetic Variants In Afmentioning

confidence: 99%

Atrial Fibrillation Genetics: Is There a Practical Clinical Value Now or in the Future?

Hucker

Saini

Lubitz

et al. 2016

Canadian Journal of Cardiology

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Atrial fibrillation (AF) is the most common sustained arrhythmia and has significant clinical impact. Over the last decade, our understanding of the genetics of AF has expanded dramatically. After a heritable predisposition for AF was identified, many investigators have in turn identified both common and rare variants associated with AF. Ongoing work is focused on translating these variants into disease pathways and novel therapeutic modalities. In this review, we focus on our understanding of the current concepts behind the genetics of AF and outline a vision for the incorporation of genetic data into clinical practice.

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Novel GATA4 mutations in lone atrial fibrillation

Cited by 27 publications

References 54 publications

Association of angiotensin-converting enzyme gene I/D and CYP11B2 gene −344T/C polymorphisms with lone atrial fibrillation and its recurrence after catheter ablation

Association of angiotensin-converting enzyme gene I/D and CYP11B2 gene −344T/C polymorphisms with lone atrial fibrillation and its recurrence after catheter ablation

Functionally significant, novelGATA4variants are frequently associated with Tetralogy of Fallot

Atrial Fibrillation Genetics: Is There a Practical Clinical Value Now or in the Future?

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