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

Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) still remains a serious issue. Ca2+ handling has a considerable effect on AF recurrence. The histidine-rich calcium-binding protein (HRC) genetic single nucleotide polymorphism (SNP), rs3745297 (T>G, Ser96Ala), is k...

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Published in:PloS one 2019-03, Vol.14 (3), p.e0213208
Main Authors: 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
Format: Article
Language:English
Subjects:
Ablation
Ablation (Surgery)
Atrial fibrillation
Atrial Fibrillation - genetics
Atrial Fibrillation - pathology
Atrial Fibrillation - therapy
Audio frequencies
Bepridil
Binding proteins
Biology and Life Sciences
Biomarkers
Calcium
Calcium (reticular)
Calcium binding proteins
Calcium ions
Calcium-binding protein
Calcium-Binding Proteins - genetics
Calmodulin
Cardiac arrhythmia
Cardiomyocytes
Cardiomyopathy
Care and treatment
Catheter Ablation - methods
Catheters
Diabetes
Diabetes mellitus
Engineering and Technology
Female
Fibrillation
Follow-Up Studies
Gene Frequency
Gene polymorphism
Genetic aspects
Genetic diversity
Genetic markers
Genetic polymorphisms
Genetic variance
Genetic variation
Genomes
Health aspects
Health sciences
Heart
Histidine
Humans
Hypertension
Kinases
Leak channels
Male
Medical instruments
Medicine
Medicine and Health Sciences
Middle Aged
Multivariate analysis
Patient outcomes
Patients
Physical Sciences
Polymorphism
Polymorphism, Single Nucleotide
Prognosis
Protein binding
Proteins
Radio frequency
Radiofrequency ablation
Recurrence
Recurrence (Disease)
Replication
Risk factors
Sarcoplasmic reticulum
Screening
Single nucleotide polymorphisms
Single-nucleotide polymorphism
University graduates
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Summary:Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) still remains a serious issue. Ca2+ handling has a considerable effect on AF recurrence. The histidine-rich calcium-binding protein (HRC) genetic single nucleotide polymorphism (SNP), rs3745297 (T>G, Ser96Ala), is known to cause a sarcoplasmic reticulum Ca2+ leak. We investigated the association between HRC Ser96Ala and AF recurrence after RFCA in paroxysmal AF (PAF) patients. We enrolled PAF patients who underwent RFCA (N = 334 for screening and N = 245 for replication) and were genotyped for HRC SNP (rs3745297). The patient age was younger and rate of diabetes and hypertension lower in the PAF patients with Ser96Ala than in those without (TT/TG/GG, 179/120/35; 64±10/60±12/59±13 y, P = 0.001; 18.5/ 9.2/8.6%, P = 0.04 and 66.1/50.0/37.1%, P = 0.001, respectively). During a mean 19 month follow-up, 57 (17.1%) patients suffered from AF recurrences. The rate of an Ser96Ala was significantly higher in patients with AF recurrence than in those without in the screening set (allele frequency model: odds ratio [OR], 1.80; P = 0.006). We also confirmed this significant association in the replication set (OR 1.74; P = 0.03) and combination (P = 0.0008). A multivariate analysis revealed that the AF duration, sinus node dysfunction, and HRC Ser96Ala were independent predictors of an AF recurrence (hazard ratio [HR], 1.04, P = 0.037; HR 2.42, P = 0.018; and HR 2.66, P = 0.007, respectively). HRC SNP Ser96Ala is important as a new genetic marker of AF recurrence after RFCA.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0213208