Sudden cardiac death (SCD) is defined as sudden unexplained death due to cardiac causes with an acute change in cardiovascular status within 1 hour of onset of symptoms. Alternatively, in unwitnessed cases, SCD can also be defined as a person last seen functionally normal 24 hours before being found dead. Despite significant advances in understanding the pathophysiology of cardiovascular diseases and the resultant improvement in resuscitation science, SCD remains a major healthcare challenge worldwide. Although the most pronounced risk factor for SCD is the presence of coronary artery disease in the setting of a depressed left ventricular function, most deaths occur in the larger, lower-risk subgroups where genetic variations and other conditions may be the precipitating factors in triggering SCD. Recently, a common genetic variation in a neuronal nitric oxide synthase regulator, nitric oxide synthase 1 adaptor protein (NOS1AP) also known as carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase protein (CAPON) gene, has been identified as a new genetic marker in modulating QT interval prolongation and SCD in general populations. Animal study revealed that NOS1AP is expressed in the heart and interacts with NOS1-NO pathways to modulate cardiac repolarization via suppressing the sarcolemmal L-type calcium current and enhancing the IKr current. This important genetic implication was soon replicated in other racial/ethnic populations and extended to a variety of clinical settings including diabetes mellitus, coronary artery disease, myocardial infarction, and congenital or drug-induced long QT syndrome. The purpose of this review aims to provide up-to-date information about the emerging new genetic marker, NOS1AP, in relation to QT prolongation and SCD.
Key words: NOS1AP; QT interval; Sudden cardiac death.