Center for Human Genetics and Laboratory Diagnostics, Dr. Klein, Dr. Rost and Colleagues

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Cytochrom P450 2D6 (CYP2D6) [T88.7]

OMIM numbers: 608902, 124030 (CYP2D6)

Dipl.-Biol. Birgit Busse

Scientific Background

CYP2D6 is involved in the metabolism of approximately 20-30% of the most common drugs, such as psychotropic drugs, neuroleptics and beta blockers. The effectiveness of tamoxifen also seems to be associated with the CYP2D6 genotype. Different variants in the CYP2D6 gene lead to a reduced or lacking enzyme activity, and to an intermediate or poor metabolizer phenotype, respectively. Under standard dose of CYP2D6 substrates, both phenotypes may develop adverse drug reactions. A reduction in dose may decrease side-effects and thus have a positive impact on treatment. Within the Central European population, the poor metabolizer alleles CYP2D6*3, *4, *5,* 6 *9 and *41 are most relevant. Within all Caucasians, the proportion of the poor metabolizer is approximately 7%, of the intermediate metabolizer approximately 40%.

The ultra-rapid metabolizer (CYP2D6*XN allele) exhibits increased enzyme activity and is associated with resistance to treatment. Under standard dose of CYP2D6 substrates, frequently no sufficient therapeutic effect is achieved (non-responder phenotype, incidence approximately 7%). In these cases, increase in dose may have a positive impact on the success of treatment.