Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024591 (malignant hyperthermia)
 2,353 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

By the introduction of technological advancement in methods of structural analysis, electronics, and recombinant DNA techniques, research in physiology has become molecular. Additionally, focus of interest has been moving away from classical physiology to become increasingly centered on mechanisms of disease. A wonderful example for this development, as evident by this review, is the field of ion channel research which would not be nearly as advanced had it not been for human diseases to clarify. It is for this reason that structure-function relationships and ion channel electrophysiology cannot be separated from the genetic and clinical description of ion channelopathies. Unique among reviews of this topic is that all known human hereditary diseases of voltage-gated ion channels are described covering various fields of medicine such as neurology (nocturnal frontal lobe epilepsy, benign neonatal convulsions, episodic ataxia, hemiplegic migraine, deafness, stationary night blindness), nephrology (X-linked recessive nephrolithiasis, Bartter), myology (hypokalemic and hyperkalemic periodic paralysis, myotonia congenita, paramyotonia, malignant hyperthermia), cardiology (LQT syndrome), and interesting parallels in mechanisms of disease emphasized. Likewise, all types of voltage-gated ion channels for cations (sodium, calcium, and potassium channels) and anions (chloride channels) are described together with all knowledge about pharmacology, structure, expression, isoforms, and encoding genes.
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PMID:Voltage-gated ion channels and hereditary disease. 1050 36

1. The conventional approach to understanding the structure and properties of ion channels has been to use physiological characterization. 2. Purification and molecular cloning of ion channel genes has enabled more detailed structure-function analyses to be undertaken. 3. An alternative approach to the identification of genes of pathophysiological importance has been the use of genetic linkage approaches and positional cloning or positional candidate analysis of ion channel genes. 4. Using genetic approaches, mutations have been described that cause inherited neurological disorders of neurons (e.g. epilepsy, migraine, deafness, ataxia and startle disease), skeletal muscle (myotonia, malignant hyperthermia, periodic paralysis and myasthenia) and cardiac muscle (long QT syndrome and ventricular fibrillation). 5. For each disease, gene structure-function analyses of the mutant alleles have provided further insights into the biology of ion channels. 6. The present brief review examines the methods used in genetic linkage studies and positional cloning of disease genes. Understanding how ion channel gene mutations give rise to dysfunctional channels will be important in defining and treating the episodic and chronic channelopathies.
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PMID:Genetics, an alternative way to discover, characterize and understand ion channels. 1115 44

There are many diseases related to ion channels. Mutations in muscle voltage-gated sodium, potassium, calcium and chloride channels, and acetylcholine-gated channel may lead to such physiological disorders as hyper- and hypokalemic periodic paralysis, myotonias, long QT syndrome, Brugada syndrome, malignant hyperthermia and myasthenia. Neuronal disorders, e.g., epilepsy, episodic ataxia, familial hemiplegic migraine, Lambert-Eaton myasthenic syndrome, Alzheimer's disease, Parkinson's disease, schizophrenia, hyperekplexia may result from dysfunction of voltage-gated sodium, potassium and calcium channels, or acetylcholine- and glycine-gated channels. Some kidney disorders, e.g., Bartter's syndrome, policystic kidney disease and Dent's disease, secretion disorders, e.g., hyperinsulinemic hypoglycemia of infancy and cystic fibrosis, vision disorders, e.g., congenital stationary night blindness and total colour-blindness may also be linked to mutations in ion channels.
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PMID:Ion channels-related diseases. 1131 Sep 70

In the last decades, advances in molecular biology have led to modern pharmacogenetics, which started as a science that focused on investigating drug metabolising enzymes and genetic determinants of pharmacokinetic variability. As more evidence has become available on the structure of drug targets and the genes coding for them, increasing attention has been directed towards pharmacodynamic explanations of variability in therapeutic response as well as in the risk for adverse drug reactions. Traditionally, genetic drug safety research has focused on variations in single genes whose functions are known to be related to given adverse drug reactions. A few such examples, malignant hyperthermia, the long QT syndrome, venous thromboembolic disease, tardive dyskinesia, and drug addiction, are presented in this article. In the future, results from the Human Genome Project together with tools such as DNA microarray technology, high-output screening systems and advanced bioinformatics, will permit a more thorough elucidation than is currently possible of the genetic components of adverse drug reactions. By screening for a large number of single nucleotide polymorphisms (SNPs), SNP patterns associated with adverse drug reactions can be discovered even though the functions of the SNPs as such are completely unknown. On the basis of these findings, it can be expected that pharmacogenetic research will identify situations where a drug should be avoided in certain individuals in order to reduce the risk for adverse drug reactions. If so, it will be feasible to use molecular diagnostics to select drugs that are safe for the individual patient.
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PMID:Genotyping of drug targets: a method to predict adverse drug reactions? 1211 41

Long QT syndrome (LQTS) is caused by a change in cardiac repolarization due to functional ion channel dysfunction which is associated with an elongation of the QT interval (hence the name) in the electrocardiogram and a predisposition to cardiac rhythm disorders (e.g. torsade de pointes, TdP) as well as cardiac events up to sudden cardiac death. There is a congenital (cLQTS) and an acquired (aLQTS) form of the disease. The prevalence of cLQTS is 1 in 2000 but aLQTS is much more common and includes a grey area due to many asymptomatic patients. The LQTS is, therefore, more common than malignant hyperthermia which is much discussed in anesthesiology and has a reported prevalence in the population of 1:3000. Considering the prevalence of both aLQTS as well as cLQTS the importance of the LQTS seems to be underestimated in current perioperative care. Potential perioperative risks of such patients can be significantly reduced by appropriate patient management. This includes adequate preoperative preparation, the correct choice of anesthetic medication as well as adequate perioperative monitoring and preparedness for immediate pharmaceutical and electrical intervention in case of typical cardiac rhythm disturbances, such as TdP arrhythmia.
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PMID:[Perioperative treatment of patients with long QT syndrome]. 2626 Jan 97