58b6c2f3-70f0-4100-999e-d1f7302341ec
title
KCNJ11  polymorphisms and sudden cardiac death in patients with acute myocardial infarction.
c5225926-b19b-4416-9320-31c24294b3c1
abstract
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.