Ser96Ala genetic variant of the human histidine-rich calcium-binding protein is a genetic predictor of recurrence after catheter ablation in patients with paroxysmal atrial fibrillation

Amioka, Michitaka; Nakano, Yukiko; Ochi, Hidenori; Onohara, Yuko; Sairaku, Akinori; Tokuyama, Takehito; Motoda, Chikaaki; Matsumura, Hiroya; Tomomori, Shunsuke; Hironobe, Naoya; Okubo, Yousaku; Okamura, Sho; Chayama, Kazuaki; Kihara, Yasuki

doi:10.1371/journal.pone.0213208

Cited by 7 publications

(9 citation statements)

References 31 publications

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“…Finally, we note that our study was largely focused on individuals of European ancestry, potentially limiting the generalizability to other ancestry groups. As illustrated in a single study on Japanese paroxysmal atrial fibrillation patients, a MAF of 26% was reported, which was similar to population data of East Asian ancestry found in gnomAD [33].…”

Section: Limitationssupporting

confidence: 80%

Lack of Evidence for the Role of the p.(Ser96Ala) Polymorphism in Histidine-Rich Calcium Binding Protein as a Secondary Hit in Cardiomyopathies

van der Voorn,

van Drie,

Proost

et al. 2023

IJMS

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Inherited forms of arrhythmogenic and dilated cardiomyopathy (ACM and DCM) are characterized by variable disease expression and age-related penetrance. Calcium (Ca2+) is crucially important for proper cardiac function, and dysregulation of Ca2+ homeostasis seems to underly cardiomyopathy etiology. A polymorphism, c.286T>G p.(Ser96Ala), in the gene encoding the histidine-rich Ca2+ binding (HRC) protein, relevant for sarcoplasmic reticulum Ca2+ cycling, has previously been associated with a marked increased risk of life-threatening arrhythmias among idiopathic DCM patients. Following this finding, we investigated whether p.(Ser96Ala) affects major cardiac disease manifestations in carriers of the phospholamban (PLN) c.40_42delAGA; p.(Arg14del) pathogenic variant (cohort 1); patients diagnosed with, or predisposed to, ACM (cohort 2); and DCM patients (cohort 3). We found that the allele frequency of the p.(Ser96Ala) polymorphism was similar across the general European–American population (control cohort, 40.3–42.2%) and the different cardiomyopathy cohorts (cohorts 1–3, 40.9–43.9%). Furthermore, the p.(Ser96Ala) polymorphism was not associated with life-threatening arrhythmias or heart failure-related events across various patient cohorts. We therefore conclude that there is a lack of evidence supporting the important role of the HRC p.(Ser96Ala) polymorphism as a modifier in cardiomyopathy, refuting previous findings. Further research is required to identify bona fide genomic predictors for the stratification of cardiomyopathy patients and their risk for life-threatening outcomes.

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Section: Limitationssupporting

confidence: 80%

Lack of Evidence for the Role of the p.(Ser96Ala) Polymorphism in Histidine-Rich Calcium Binding Protein as a Secondary Hit in Cardiomyopathies

van der Voorn,

van Drie,

Proost

et al. 2023

IJMS

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“…A study showed that the human HRC variant Ser96Ala was overexpressed in cardiomyocytes by gene transfer to adenovirus, resulting in increased SR Ca 2+ overload and Ca 2+ spark frequency [134]. Japanese scholar Amioka et al [26] recruited 334 patients with paroxysmal AF who underwent radiofrequency ablation and found that HRC SNP rs3745297 (Ser96Ala) was an independent risk factor for AF recurrence by multifactorial regression analysis. The frequency of minor allele G was significantly higher in the recurrence group than in the nonrecurrence group (allele frequency model OR 1.8, p = 0.006; recessive model OR 3.55, p = 0.0009).…”

Section: Hrc Snp Rs3745297 (T > G Ser96ala)mentioning

confidence: 99%

Gene Polymorphism and Recurrent Atrial Fibrillation after Catheter Ablation: A Comprehensive Review

Wang¹,

Xue²,

Shi³

et al. 2023

Rev. Cardiovasc. Med.

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Atrial fibrillation (AF) is one of the most common cardiac arrhythmias, but its pathogenesis is still poorly understood. Catheter ablation is one of the most effective treatments for AF, but recurrence after ablation remains a challenge. There has been much research into the association of AF recurrence with several factors, including genetics. Over the past decade or so, significant advances have been made in the genetic architecture of atrial fibrillation. Genome-wide association studies (GWAS) have identified over 100 loci for genetic variants associated with atrial fibrillation. However, there is relatively little information on the systematic assessment of the genes related to AF recurrence after ablation. In this review article, we highlight the value of genetic polymorphisms in atrial fibrillation recurrence after catheter ablation and their potential mechanisms in the recurrence process to enhance our understanding of atrial fibrillation recurrence and contribute to individualized treatment strategies for patients with AF.

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“… 105 A histidine-rich calcium-binding protein SNP (rs3745297) was associated with a recurrence after CA in a Japanese cohort of 382 patients. 106 …”

Section: Genetic Basis Of Afmentioning

confidence: 99%

Genetics of atrial fibrillation—practical applications for clinical management: if not now, when and how?

Kany

Reißmann

Metzner

et al. 2021

Cardiovascular Research

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The prevalence and economic burden of atrial fibrillation (AF) are predicted to more than double over the next few decades. In addition to anticoagulation and treatment of concomitant cardiovascular conditions, early and standardized rhythm control therapy reduces cardiovascular outcomes as compared with a rate control approach, favoring the restoration and maintenance of sinus rhythm safely. Current therapies for rhythm control of AF include anti-arrhythmic drugs (AAD) and catheter ablation (CA). However, response in an individual patient is highly variable with some remaining free of AF for long periods on antiarrhythmic therapy, while others require repeat AF ablation within weeks. The limited success of rhythm control therapy for AF is in part related to incomplete understanding of the pathophysiological mechanisms and our inability to predict responses in individual patients. Thus, a major knowledge gap is predicting which patients with AF are likely to respond to rhythm control approach. Over the last decade, tremendous progress has been made in defining the genetic architecture of AF with the identification of rare mutations in cardiac ion channels, signaling molecules and myocardial structural proteins associated with familial (early-onset) AF. Conversely, genome-wide association studies (GWAS) have identified common variants at over 100 genetic loci and the development of polygenic risk scores has identified high-risk individuals. Although retrospective studies suggest that response to AADs and CA is modulated in part by common genetic variation, the development of a comprehensive clinical and genetic risk score may enable the translation of genetic data to the bedside care of AF patients. Given the economic impact of the AF epidemic, even small changes in therapeutic efficacy may lead to substantial improvements for patients and health care systems.

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Ser96Ala genetic variant of the human histidine-rich calcium-binding protein is a genetic predictor of recurrence after catheter ablation in patients with paroxysmal atrial fibrillation

Cited by 7 publications

References 31 publications

Lack of Evidence for the Role of the p.(Ser96Ala) Polymorphism in Histidine-Rich Calcium Binding Protein as a Secondary Hit in Cardiomyopathies

Lack of Evidence for the Role of the p.(Ser96Ala) Polymorphism in Histidine-Rich Calcium Binding Protein as a Secondary Hit in Cardiomyopathies

Gene Polymorphism and Recurrent Atrial Fibrillation after Catheter Ablation: A Comprehensive Review

Genetics of atrial fibrillation—practical applications for clinical management: if not now, when and how?

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