Evaluating Common Variants in NOS1AP in Patients with Implantable Cardioverter Defibrillator for Secondary Prevention

Abstract Background Contemporary researchers found single nucleotide polymorphisms (SNPs) in nitric oxide synthase 1 adaptor protein (NOS1AP) gene are associated with altered QT intervals and SCD. However, the clinical utility and implications of these SNP have not been described. This study aims to explore the clinical utility and implications of SNPs in nitric oxide synthase 1 adaptor protein (NOS1AP) in patients with implantable cardioverter defibrillator (ICD) for secondary prevention. Methods We firstly conducted a case-control study to evaluate the associations between hot-spot SNPs in NOS1AP (rs12143842, rs10494366, rs12567209 and rs16847548) and patients with ICD for secondary prevention. Then the clinical values of the positive SNPs were further evaluated in these patients. All patients were divided into three groups according to different genotypes of the positive SNPs. ICD interrogation data at 3, 12 months, and 3 years after implantation, which include rapid ventricular arrhythmia episodes and appropriate therapies, were analyzed in three genotypes. Results Case-control study revealed significant allelic association between rs10494366 and ICD recipients who experienced appropriate therapies. After a mean follow-up time of 31.70 ± 9.15 months, we detected not only significant difference among three genotypes on the distribution of ICD shocks and appropriate therapies, but apparently also the correlation of rs10494366 and ICD shocks. Furthermore, under kaplan-meier and cox regression analysis, TT genotype both showed higher risk for sudden cardiac death (SCD) compared with GG genotype. Conclusions The present study revealed that SNP rs10494366 was associated with appropriate therapies and SCD in patients with ICD for secondary prevention for the first time.