Clinical Applications of Genomics : Pharmacogenomics
Pharmacogenomics is the study of the influence of genetic variation on a person's response to a drug. This influence may occur through the effect of genetic variation on drug levels (pharmacokinetics) or through genetic variation of the target of a drug (pharmacodynamics), and it can lead to a change in the efficacy or a change in the adverse effects (toxicity) of the drug.
Genetic testing may help to predict whether a drug will have little or no efficacy. Proteins can influence the active level of drugs by influencing absorption, activation, inactivation, cellular transport, or elimination. The influence of genetic variation on drug activation is illustrated by the example of cytochrome p450 2D6 (CYP2D6). CYP2D6 enzyme is needed to activate the pro-drug codeine into the metabolite morphine, which in turn is responsible for pain relief. Genetic testing may reveal that a person has inherited a variant of CYP2D6 enzyme with little or no function; thus, this person will have little pain relief from codeine.7 Hence, genetic testing may help to predict whether a drug will have little or no effect in a patient, thereby avoiding the use of an ineffective drug.
Genetic testing may also help to predict drug toxicity. For example, the thiopurine S-methyltransferase (TPMT) enzyme is needed to inactivate toxic drugs such as 6-mercaptopurine. Genetic testing may reveal that a person has an inherited variation that leads to low TPMT activity. The "usual" dose of mercaptopurine may be life-threatening in this person.8 Thus the dose of mercaptopurine should be greatly reduced in persons with TPMT deficiency. Conversely, patients with high TPMT activity will not have the desired therapeutic effect with the "usual" dose of mercaptopurine and would need higher than "usual" doses.
