The last decade has seen a dramatic increase in the understanding of the molecular basis of arrhythmias. Much of this new information has been driven by genetic studies that focused on rare, monogenic arrhythmia syndromes that were accompanied or followed by cellular electrophysiological or biochemical studies. The marked clinical heterogeneity known from these familial arrhythmia syndromes has led to the development of a multifactorial (multi-hit) concept of arrhythmogenesis in which causal gene mutations have a major effect on disease expression that is further modified by other factors such as age, gender, sympathetic tone, and environmental triggers. Systematic genetic studies have unraveled an unexpected DNA sequence variance in these arrhythmia genes that has ethnic-specific patterns. Whether this genetic variance may contribute as a second genetic modifier for arrhythmia development is under current investigation. The aim of this article is to review common genetic variation in ion channel genes and to compare these recent findings.

Myocardial β-adrenergic receptors (βARs) are important in altering heart rate, inotropic state, and myocardial relaxation (lusitropy). The β1AR and β2AR stimulation increases cyclic adenosine monophosphate concentration with the net result of myocyte contraction, whereas β3AR stimulation results in decreased inotropy. Downregulation of β1ARs in heart failure, as well as an increased β3AR activity and density, lead to decreased cyclic adenosine monophosphate production and reduced inotropy. The βAR antagonists are commonly used in patients with coronary artery disease and heart failure; however, perioperative use of βAR antagonists is controversial. Individual patient's response to beta-blocker therapy is an area of intensive research, and apart from pharmacokinetics, pharmacodynamics, and ethnic differences, genetic alterations have become more important in the last 20 years. The most common genetic variants in humans are single nucleotide polymorphisms (SNPs). There are 2 clinically relevant SNPs for the β1AR (Ser49Gly, Arg389Gly), 3 for the β2AR (Arg16Gly, Gln27Glu, Thr164Ile), and 1 for the β3AR (Trp64Arg). Although results are somewhat controversial, generally large datasets have the potential to show a relationship between βAR SNPs and outcomes such as development and progression of heart failure, coronary artery disease, vascular reactivity, hypertension, asthma, obesity, and diabetes. Although βAR SNPs may not directly cause disease, they appear to be risk factors for, and modifiers of, disease and the response to stress and drugs. In the perioperative setting, this has specifically been demonstrated for the Arg389Gly β1AR polymorphism with which patients with the Gly variant had a higher incidence of adverse perioperative events. Knowing that genetic variants play an important role, perioperative medicine will likely change from simple therapeutic intervention to a more personalized way of adrenergic receptor modulation.

Myocardial β-adrenergic receptors (βARs) are important in altering heart rate, inotropic state, and myocardial relaxation (lusitropy). The β1AR and β2AR stimulation increases cyclic adenosine monophosphate concentration with the net result of myocyte contraction, whereas β3AR stimulation results in decreased inotropy. Downregulation of β1ARs in heart failure, as well as an increased β3AR activity and density, lead to decreased cyclic adenosine monophosphate production and reduced inotropy. The βAR antagonists are commonly used in patients with coronary artery disease and heart failure; however, perioperative use of βAR antagonists is controversial. Individual patient's response to beta-blocker therapy is an area of intensive research, and apart from pharmacokinetics, pharmacodynamics, and ethnic differences, genetic alterations have become more important in the last 20 years. The most common genetic variants in humans are single nucleotide polymorphisms (SNPs). There are 2 clinically relevant SNPs for the β1AR (Ser49Gly, Arg389Gly), 3 for the β2AR (Arg16Gly, Gln27Glu, Thr164Ile), and 1 for the β3AR (Trp64Arg). Although results are somewhat controversial, generally large datasets have the potential to show a relationship between βAR SNPs and outcomes such as development and progression of heart failure, coronary artery disease, vascular reactivity, hypertension, asthma, obesity, and diabetes. Although βAR SNPs may not directly cause disease, they appear to be risk factors for, and modifiers of, disease and the response to stress and drugs. In the perioperative setting, this has specifically been demonstrated for the Arg389Gly β1AR polymorphism with which patients with the Gly variant had a higher incidence of adverse perioperative events. Knowing that genetic variants play an important role, perioperative medicine will likely change from simple therapeutic intervention to a more personalized way of adrenergic receptor modulation.

Myocardial β-adrenergic receptors (βARs) are important in altering heart rate, inotropic state, and myocardial relaxation (lusitropy). The β1AR and β2AR stimulation increases cyclic adenosine monophosphate concentration with the net result of myocyte contraction, whereas β3AR stimulation results in decreased inotropy. Downregulation of β1ARs in heart failure, as well as an increased β3AR activity and density, lead to decreased cyclic adenosine monophosphate production and reduced inotropy. The βAR antagonists are commonly used in patients with coronary artery disease and heart failure; however, perioperative use of βAR antagonists is controversial. Individual patient's response to beta-blocker therapy is an area of intensive research, and apart from pharmacokinetics, pharmacodynamics, and ethnic differences, genetic alterations have become more important in the last 20 years. The most common genetic variants in humans are single nucleotide polymorphisms (SNPs). There are 2 clinically relevant SNPs for the β1AR (Ser49Gly, Arg389Gly), 3 for the β2AR (Arg16Gly, Gln27Glu, Thr164Ile), and 1 for the β3AR (Trp64Arg). Although results are somewhat controversial, generally large datasets have the potential to show a relationship between βAR SNPs and outcomes such as development and progression of heart failure, coronary artery disease, vascular reactivity, hypertension, asthma, obesity, and diabetes. Although βAR SNPs may not directly cause disease, they appear to be risk factors for, and modifiers of, disease and the response to stress and drugs. In the perioperative setting, this has specifically been demonstrated for the Arg389Gly β1AR polymorphism with which patients with the Gly variant had a higher incidence of adverse perioperative events. Knowing that genetic variants play an important role, perioperative medicine will likely change from simple therapeutic intervention to a more personalized way of adrenergic receptor modulation.

Myocardial β-adrenergic receptors (βARs) are important in altering heart rate, inotropic state, and myocardial relaxation (lusitropy). The β1AR and β2AR stimulation increases cyclic adenosine monophosphate concentration with the net result of myocyte contraction, whereas β3AR stimulation results in decreased inotropy. Downregulation of β1ARs in heart failure, as well as an increased β3AR activity and density, lead to decreased cyclic adenosine monophosphate production and reduced inotropy. The βAR antagonists are commonly used in patients with coronary artery disease and heart failure; however, perioperative use of βAR antagonists is controversial. Individual patient's response to beta-blocker therapy is an area of intensive research, and apart from pharmacokinetics, pharmacodynamics, and ethnic differences, genetic alterations have become more important in the last 20 years. The most common genetic variants in humans are single nucleotide polymorphisms (SNPs). There are 2 clinically relevant SNPs for the β1AR (Ser49Gly, Arg389Gly), 3 for the β2AR (Arg16Gly, Gln27Glu, Thr164Ile), and 1 for the β3AR (Trp64Arg). Although results are somewhat controversial, generally large datasets have the potential to show a relationship between βAR SNPs and outcomes such as development and progression of heart failure, coronary artery disease, vascular reactivity, hypertension, asthma, obesity, and diabetes. Although βAR SNPs may not directly cause disease, they appear to be risk factors for, and modifiers of, disease and the response to stress and drugs. In the perioperative setting, this has specifically been demonstrated for the Arg389Gly β1AR polymorphism with which patients with the Gly variant had a higher incidence of adverse perioperative events. Knowing that genetic variants play an important role, perioperative medicine will likely change from simple therapeutic intervention to a more personalized way of adrenergic receptor modulation.

Myocardial β-adrenergic receptors (βARs) are important in altering heart rate, inotropic state, and myocardial relaxation (lusitropy). The β1AR and β2AR stimulation increases cyclic adenosine monophosphate concentration with the net result of myocyte contraction, whereas β3AR stimulation results in decreased inotropy. Downregulation of β1ARs in heart failure, as well as an increased β3AR activity and density, lead to decreased cyclic adenosine monophosphate production and reduced inotropy. The βAR antagonists are commonly used in patients with coronary artery disease and heart failure; however, perioperative use of βAR antagonists is controversial. Individual patient's response to beta-blocker therapy is an area of intensive research, and apart from pharmacokinetics, pharmacodynamics, and ethnic differences, genetic alterations have become more important in the last 20 years. The most common genetic variants in humans are single nucleotide polymorphisms (SNPs). There are 2 clinically relevant SNPs for the β1AR (Ser49Gly, Arg389Gly), 3 for the β2AR (Arg16Gly, Gln27Glu, Thr164Ile), and 1 for the β3AR (Trp64Arg). Although results are somewhat controversial, generally large datasets have the potential to show a relationship between βAR SNPs and outcomes such as development and progression of heart failure, coronary artery disease, vascular reactivity, hypertension, asthma, obesity, and diabetes. Although βAR SNPs may not directly cause disease, they appear to be risk factors for, and modifiers of, disease and the response to stress and drugs. In the perioperative setting, this has specifically been demonstrated for the Arg389Gly β1AR polymorphism with which patients with the Gly variant had a higher incidence of adverse perioperative events. Knowing that genetic variants play an important role, perioperative medicine will likely change from simple therapeutic intervention to a more personalized way of adrenergic receptor modulation.

Long-QT syndrome (LQTS) is characterized by such striking clinical heterogeneity that, even among family members carrying the same mutation, clinical outcome can range between sudden death and no symptoms. We investigated the role of genetic variants as modifiers of risk for cardiac events in patients with LQTS.

Myocardial β-adrenergic receptors (βARs) are important in altering heart rate, inotropic state, and myocardial relaxation (lusitropy). The β1AR and β2AR stimulation increases cyclic adenosine monophosphate concentration with the net result of myocyte contraction, whereas β3AR stimulation results in decreased inotropy. Downregulation of β1ARs in heart failure, as well as an increased β3AR activity and density, lead to decreased cyclic adenosine monophosphate production and reduced inotropy. The βAR antagonists are commonly used in patients with coronary artery disease and heart failure; however, perioperative use of βAR antagonists is controversial. Individual patient's response to beta-blocker therapy is an area of intensive research, and apart from pharmacokinetics, pharmacodynamics, and ethnic differences, genetic alterations have become more important in the last 20 years. The most common genetic variants in humans are single nucleotide polymorphisms (SNPs). There are 2 clinically relevant SNPs for the β1AR (Ser49Gly, Arg389Gly), 3 for the β2AR (Arg16Gly, Gln27Glu, Thr164Ile), and 1 for the β3AR (Trp64Arg). Although results are somewhat controversial, generally large datasets have the potential to show a relationship between βAR SNPs and outcomes such as development and progression of heart failure, coronary artery disease, vascular reactivity, hypertension, asthma, obesity, and diabetes. Although βAR SNPs may not directly cause disease, they appear to be risk factors for, and modifiers of, disease and the response to stress and drugs. In the perioperative setting, this has specifically been demonstrated for the Arg389Gly β1AR polymorphism with which patients with the Gly variant had a higher incidence of adverse perioperative events. Knowing that genetic variants play an important role, perioperative medicine will likely change from simple therapeutic intervention to a more personalized way of adrenergic receptor modulation.