Pharmacogenetics – five decades of therapeutic lessons from genetic diversity

ABSTRACT Physicians have long been aware of the subtle differences in the responses of patients to medication. The recognition that a part of this variation is inherited, and therefore

predictable, created the field of pharmacogenetics fifty years ago. Knowing the gene variants that cause differences among patients has the potential to allow 'personalized' drug

therapy and to avoid therapeutic failure and serious side effects. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution

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1989). Google Scholar  Download references ACKNOWLEDGEMENTS Research in the author's laboratory is supported by the Swiss National Science Foundation. AUTHOR INFORMATION AUTHORS AND

AFFILIATIONS * Biozentrum, University of Basel, Basel, CH-4056, Switzerland Urs A. Meyer Authors * Urs A. Meyer View author publications You can also search for this author inPubMed Google

Scholar ETHICS DECLARATIONS COMPETING INTERESTS The author declares no competing financial interests. RELATED LINKS RELATED LINKS DATABASES ENTEZ AhR CAR _CYP2C9_ CYP2C19 CYP2D6 G6PD _NAT2_

TPMT UGT1A1 Home Page of the _CYP_ Allele Nomenclature Committee International HapMap Project Arylamine _N_-Acetyltransferase (NAT) Nomenclature GLOSSARY * ALCAPTONURIA A rare inherited

disorder of metabolism that is characterized by urine which turns black when exposed to air. * ANTI-ARRHYTHMICS Medicines that are used to treat patients who have irregular heart rhythms. *

APNEA The absence of breathing (respirations). * CHEMICAL INDIVIDUALITY Garrod's influential idea that 'factors which confer upon us our predisposition and immunities from disease

are inherent in our very chemical structure, and even in the molecular groupings which went to the making of the chromosomes from which we sprang.' * DIPLOPIA Double vision. Usually due

to misalignment of the eyes. * FAMILIAL DYSAUTONOMIA A disorder of the autonomic nervous system that is inherited as an autosomal recessive trait and is characterized by several sensory

deficits (as of taste and pain), excessive sweating and salivation, lack of tears, difficulty in swallowing and many other symptoms. * HYPERBILIRUBINEMIA Abnormally high levels of bilirubin

in the blood. * ISONIAZID An anti-bacterial drug that has been used to prevent and to treat tuberculosis since 1952. * MALIGNANT HYPERTHERMIA A group of inherited muscle problems

characterized by muscle breakdown following certain stimuli — such as anesthesia, extremes of exercise (particularly in hot conditions), fever, or use of stimulant drugs. The problems

associated with this condition result from over-excitable muscles that contract uncontrollably, severe fever, abnormal heart rhythms, and kidney failure. * MEPHENYTOIN An anticonvulsant that

is indicated for the treatment of tonic-clonic and partial seizures in patients who are not controlled with less-toxic medications. * METHEMOGLOBINEMIA An inherited blood disorder that is

characterized by increased levels of an abnormal form of haemoglobin that is unable to deliver oxygen effectively. * NORTRIPTYLINE An antidepressant medication of the tricyclic class.

Medications in this class are often referred to as tricyclic antidepressants, or TCAs. * OPIOIDS Synthetic opium-like drugs that possess some affinity for any, or all, of the opioid-receptor

subtypes. Common opioids are endorphin, fentanyl and methadone. * OXYTOXIC A drug that is useful in starting or aiding in labour. Also used to stimulate uterine contractions. * PERIPHERAL

NEUROPATHY A problem in peripheral nerve function (any part of the nervous system except the brain and spinal cord) that causes pain, numbness, tingling, swelling, and muscle weakness in

various parts of the body. Neuropathies might be caused by physical injury, infection, toxic substances, disease (for example, cancer, diabetes, kidney failure, or malnutrition), or drugs

such as anticancer drugs. * PHARMACODYNAMICS The process of interaction of pharmacologically active substances with target sites, and the biochemical and physiological consequences leading

to therapeutic or adverse effects. * PHARMACOKINETICS The rocess of the uptake of drugs by the body, the biotransformation they undergo, the distribution of the drugs and their metabolites

in the tissues, and the elimination of the drugs and their metabolites from the body. * PORPHYRIA A group of disorders that are characterized by the excessive production of porphyrins or

their precursors, and which arise from abnormalities in the regulation of the porphyrin–heme pathway. Acquired pophyrias, which are due to inhibition of enzymes in the metabolic pathway by a

drug, toxin or abnormal metabolite, are more common than those that are inherited. * PSEUDOCHOLINESTERASE DEFICIENCY A rare genetic disorder that causes an absence of the plasma enzyme

pseudocholinesterase, which can cause respiratory difficulty during surgery if the muscle-relaxing drug succinylcholine is used. * SYMPATHICOLYTIC Interfering with, opposing, inhibiting, or

destroying impulses from the sympathetic nervous system. * WARFARIN An oral anticoagulant that inhibits the synthesis of clotting factors, thus preventing blood-clot formation. RIGHTS AND

PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Meyer, U. Pharmacogenetics – five decades of therapeutic lessons from genetic diversity. _Nat Rev Genet_ 5, 669–676

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