PII‐25

BACKGROUND/AIMS Cytochrome P450 enzymes play an important role in the therapeutic effect of currently prescribed drugs including antiarrhythmics, antidepressants, and morphine derivatives. The highly polymorphic CYP2D6 ( 2D6 ) gene locus manifests variations in enzymatic activity that affect phenotype. Ultrarapid metabolizers are a target of study as they often exhibit therapeutic failure or inefficacy. The purpose of this study was to characterize the allelic variants found within 2D6 gene duplications and to derive allelic frequency data across different ethnic groups. METHODS 227 subjects were screened for the presence of a 2D6 gene duplication using long‐range PCR. DNA from subjects who were 2D6 duplication‐positive was subjected to a second long‐range PCR specific for the duplicated region, which was then used as a template for PCR and/or sequencing for allelic identification of the 2D6 duplication. RESULTS We have identified several different 2D6 allelic duplications. Further analysis has revealed subjects that have duplicated non‐functional alleles including *4xN and *6xN . Continued testing is currently underway to establish frequency information for each type of duplication and to correlate frequencies among different ethnic groups. CONCLUSIONS In order to fully understand the effect that 2D6 gene duplications have on phenotype, it is important to know which allelic variant is being duplicated. For the subjects examined, we have identified which alleles are duplicated. Clinical Pharmacology & Therapeutics (2005) 79 , P43–P43; doi: 10.1016/j.clpt.2005.12.150