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Background  Atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA) still remains a serious issue. Ca 2+  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 Ca 2+  leak. We investigated the association between  HRC  Ser96Ala and AF recurrence after RFCA in paroxysmal AF (PAF) patients.    Methods and results  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).    Conclusion   HRC  SNP Ser96Ala is important as a new genetic marker of AF recurrence after RFCA.

plos one

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