Pharmacogenomic Screening for Depressed Children and Adolescents
While the utilization of clinical genotyping to determine drug response and dosage has been anticipated for many years, the actual utilization of screening for atypical drug metabolizers has only recently become a reality. What is the promise of this technology, as well as the limitations?
Psychiatric Times
August 2005
Vol. XXII
Issue 9
While the utilization of clinical genotyping to determine drug response and dosage has been anticipated for many years, the actual utilization of screening for atypical drug metabolizers has only recently become a reality. The key factor making this innovation possible has been the development of low-cost, high-throughput genotyping that can accurately establish the precise genotype of key drug metabolizing enzymes (DME). In the very near future, more complex methodologies to ascertain the influence of both DME genes and genes that code for key drug targets will be available. However, today it is possible to improve the likelihood of a positive therapeutic outcome as well as minimize adverse drug effects for select children and adolescents who are being treated for depression.
At this point in the development of psychiatric pharmacogenomics, the most frequently screened DME gene is cytochrome P450 (CYP) 2D6. Genotyping of the 2D6 gene is available through most large reference laboratories. For example, clinical testing of the 2D6 genotype was initiated at the Mayo Clinic in February 2003.
One important consideration in pharmacogenomic clinical genotyping is the accuracy and comprehensiveness of the assessment. The 2D6 gene is highly variable, having 180 reported variants. The vast majority of these variants are extremely rare, but there are 11 different alleles that occur in significant numbers of patients throughout the world.
This gene is located on the long arm of the 22nd chromosome in an area that is referred to as a "hot spot." It is a hot spot because there is an increased probability for the occurrence of "uneven crossovers" at this location, and as a consequence, there has been an accumulation of multiple copies of this gene on this chromosome. The wide variation in the 2D6 gene demonstrates that the protein product is not a critical enzyme required for survival.
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