( Michael S. Singer M.D. Ph.D. Contr...)Gene Chips to Detect CYP Variations: A New Step Toward Customized Medical Therapy.,Health

The FDA approval of BiDil for heart failure in African American patients has underscored the concept that two patients can respond differently to the same medication. This concept holds true for a wide variety of everyday medications, and in many cases is due to individual genetic variations. As the field of pharmacogenetics focuses on these issues, valuable new laboratory tools have arrived to help clinicians apply pharmacogenetic knowledge to patient care.

Probably the most important gene family to govern individual drug responses, CYP (also called cytochrome P450) oxidases are a diverse family of enzymes that metabolize compounds unfamiliar to the body. Concentrated in liver cells, they modify the chemical structure of drugs shortly after they are absorbed from the gastrointestinal tract. The chemical modification renders them more water soluble and hence more easily excreted. Six CYP enzymes (named 1A2, 2C9, 2C19, 2D6, 2E1, 3A4) account for over 90% of drug metabolism (but do not appear to account for the selectivity of BiDil). Since a patient can take several concurrent medications metabolized by the same CYP enzyme, it should come as no surprise that CYP-related drug interactions are common. Clinicians are generally aware of these interactions, which either involve inhibition (competition) between two or more medications for the same enzyme, or induction (increase) of a particular CYP enzymes activity in response to a particular medication. In the former scenario, blood concentrations and the risk of side effects can rise to perilous levels; in the latter, concentrations can decline to the point that therapeutic value is lost.

Patients can also carry mutations or duplications in one or more CYP enzymes. Usually unbeknownst to the clinician, these polymorphisms can have pronounced effects on a patients ability to met
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