The effect of genes on our phenotype as well as the existence of hereditary disease has been known for a long time. However, another effect genes can have on our health has only come to attention recently: the effect of genes on drug metabolism.
Pharmacogenetics or pharmacogenomics?
Pharmacogenetics is traditionally defined as study of effects of hereditability on drug metabolism. With the recent fashion of adding –omics to wider areas of research the term pharmacogenomics was coined. While these are sometimes used interchangeably pharmacogenomics and pharmacogenetics do not refer to the same thing. Pharmacogentics studies the effect of specific genes on drug metabolism while pharmacogenomics as a broader term includes effect all genes in the genome may have on drug metabolism. It is considered to be an important area of research that could be the key to improving healthcare.
Pirmohamed M. (2001). Pharmacogenetics and pharmacogenomics. British journal of clinical pharmacology, 52(4), 345-7.
Early observations made on differences in drug metabolism due to biochemical individuality date as far back as 1930s. However, pharmacogenetics field was officially recognized only in 1959 when the term was first published by German physician Friedrich Vogel in response to earlier observations of interindividual variability in phenylthiocarbamide taste perception and isolated cases of drug-induced porphyria. Other important discoveries that were made during this time include identification of primaquine-induced hemolytic anemia among African-Americans (later shown to be due to glucose-6-phosphate dehydrogenase [G6PD] variant alleles), succinylcholine-induced prolonged apnea during anesthesia (due to autosomal recessive butyrylcholinesterase deficiency), and severe adverse effects after antituberculosis treatment with isoniazid (later shown to be due to N-acetyltransferase [NAT2] variant alleles). Apart from Vogel´s article two other significant publications of that time were the American Medical Association-initiated review of available pharmacogenetic studies by Arno Motulsky and the first textbook dedicated to the discipline in 1962 by Werner Kalow.
Scott S. A. (2011). Personalizing medicine with clinical pharmacogenetics. Genetics in medicine : official journal of the American College of Medical Genetics, 13(12), 987-95.
The most influential discovery that brought the clinical use of pharmacogenetics to light was the discovery of the hepatic cytochrome P450 oxidase that controls debrisoquine and sparteine metabolism in 1977. The produced enzyme CYPD6 was purified, studied and sequenced and is believed to be involved in metabolism of 25% of drugs. More than 80 variant CYP2D6 alleles have since been discovered worldwide, many of which encode deficient enzyme activity, and these are carefully cataloged by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee. CYPD6 genotypes were eventually shown to correlate with thefour general metabolism phenotypes: ultrarapid, extensive, intermediate, and poor (Figure 1). Since clinical DNA-based CYP2D6 testing was made available, interpretation of a patient’s genotype typically includes one of these predicted metabolism phenotypes although it should be noted that this still a prediction that is not based on individual measurements.