KCNJ11 polymorphisms and sudden cardiac death in patients with acute myocardial infarction

Purpose. - Patients with an acute myocardial infarction (AMI) are of high risk to develop ischemia-induced ventricular arrhythmias, leading to sudden cardiac death (SCD) in about one third of all AMI patients. The individual susceptibility to ischemia-induced arrhythmias may be modified by polymorphisms in genes encoding ion channels. The cardiac ATP-dependent potassium channel (K_ATP) current is generated by ion channels encoded by the KCNJ11 gene and the SUR2a gene. Opening of the K_ATP channel during ischemia results in action potential shortening in various studies and may therefore influence the outcome of AMI patients. Methods. - Using a three-primer strategy, we sequenced the complete coding and adjacent 5′ and 3′ sequences of the intronless KCNJ11 gene (1.3 kb) prospectively in two groups. Patients of group 1 (n=84) survived three or more transmyocardial infarctions without developing any ventricular arrhythmias. Patients of group 2 died suddenly from their first myocardial infarction (n=86), most of them witnessed SCDs. Results. - We identified a total of six known polymorphisms (K23E, A190A, L267V, L270V, I337V, and K281K) and two new polymorphisms (L267L, 3′UTR +62 G/A). The allele, genotype, and haplotype frequencies did not differ between the two groups. All polymorphisms were found to be in Hardy-Weinberg equilibrium. In addition, we identified two novel missense mutations in a highly conserved region of the gene in two patients of group 2 (P266T and R371H) with yet unknown functional consequences. Conclusion. - In this study of AMI patients, SCD was not related to polymorphisms in the KCNJ11 gene.