Insights into the genome-wide association studies of the electrocardiographic early repolarization pattern

Abstract

s The presence of J waves and ST-segment elevations on the electrocardiogram (ECG), today commonly termed the early repolarization pattern (ERP), was first described by Grant et al back in 1951. In the following decades, it was onsidered a normal ECG variant but this assumption was ramatically changed in 2008 when 2 groups reported a igh prevalence of ERP in patients with idiopathic ventriclar fibrillation and sudden cardiac death. The ERP is a common ECG finding, more common in African Americans and athletes, and is found in 1%–13% of the general population. Although no consensus definition exists, ERP has previously been defined by a J wave or J point (QRS-ST junction) of at least 1 mm (0.1 mV) in at least 2 contiguous leads in the inferior leads (II, III, aVF), lateral leads (I, aVL, and V4-V6), or both. Today, the association between ERP and life-threatening arrhythmias has generally led to the entity termed early repolarization syndrome (ERS)—also termed the “J-wave syndromes”—by some authors. Most recently, ERP has been divided into subtypes in order to identify the pathologic variants. The horizontal or descending ST segment confers to the highest risk of arrhythmic death. The inheritable component of the ERP has slowly come into focus in recent years. In the Framingham Heart Study, siblings of ERP subjects had twice the likelihood of a ERP than non-ERP subjects. Furthermore, in a German tudy, ERP was around twice as likely if one parent was iagnosed with the disease. Recently, variants in 6 genes have been associated with ERP/ERS: KCNJ8, CACNA1C, CACNB2b, CACNA2D1, BCC9, and SCN5A. These genes encode the sodium, otassium, and calcium currents, and it is hypothesized hat changes in the cellular repolarization pattern give ise to the characteristic surface ECG. These genes have