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Pharmacogenetics – five decades of therapeutic lessons from genetic diversity

Nature Reviews Genetics volume 5, pages 669–676 (2004)Cite this article

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.

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Figure 1: Appearance of the terms pharmacogenetics and pharmacogenomics in publications in PUBMED (National Library of Medicine).
Figure 2: Sir Archibald E. Garrod (1958–1936).
Figure 3: Genotype–phenotype relationships of the CYP2D6-polymorphism.

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Acknowledgements

Research in the author's laboratory is supported by the Swiss National Science Foundation.

Author information

Authors and Affiliations

  1. Biozentrum, University of Basel, Basel, CH-4056, Switzerland

    Urs A. Meyer

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  1. Urs A. Meyer
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Related links

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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.

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Meyer, U. Pharmacogenetics – five decades of therapeutic lessons from genetic diversity. Nat Rev Genet 5, 669–676 (2004). https://doi.org/10.1038/nrg1428

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