Bifid T waves on the ECG and genetic variation in calcium channel voltage‐dependent beta 2 subunit gene ( CACNB2 ) in acute Kawasaki disease

Background We previously described the association of genetic variants in calcium channel genes and susceptibility to Kawasaki disease (KD), an acute, self‐limited vasculitis, and the most common cause of acquired cardiac disease in children. Abnormal repolarization of cardiomyocytes and changes in T wave morphology have been reported in KD but have not been studied systematically. Methods We analyzed acute and convalescent ECG T wave morphology in two independent cohorts of KD subjects and studied the association between bifid T waves and genetic variants in previously reported genes with SNVs associated with cardiac repolarization. Results Bifid T waves in limb leads were identified in 24% and 27% of two independent cohorts of acute KD subjects. C alcium channel voltage‐dependent beta 2 subunit gene ( CACNB2 ) (rs1409207) showed association with bifid T waves in both cohorts (nominal P = .04 and P = .0003, respectively). This CACNB2 polymorphism also showed association with KD susceptibility in a previously published KD genome wide association study data (nominal P = .009). Conclusion This genotype/phenotype association study uncovered a variant in CACNB2 that may be associated with both KD susceptibility and bifid T waves, a novel signature of altered myocardial repolarization. The present study combined with published reports suggests that genetic variants in calcium channels and intracellular calcium signaling play a prominent role in shaping susceptibility to KD.