A gene with at least 75 different major alleles.
Located on chromosome 22.
Alleles confer variability in the enzyme activity of the CYP2D6 system.
Some of the alleles have reduced or absent enzyme functions.
6-10% of Caucasians inherit two alleles of CYP2P6 with polymorphisms and or a deletion, leading to limited or no protein expression.
CYP2D6 polymorphisms and deletions are rare in East Asians and Africans.
Patients with normal range of CYP2D6 activity represents 75-92% of the population.
Patients with normal range of CYP2D6 activity are called extensive metabolizers.
Approximately 5-10% of the population are poor metabolizers who have no functional alleles.
Ultra rapid metabolizers have two or more functional alleles and can cause drug toxicity.
The presence of ultra-rapid metabolizers varies by ethnic group: lower than 1% among Chinese and Japanese, and approximately 15% among Middle Eastern North African patients.
Rapid metabolizes may be at risk for increased toxicity from codeine activation to morphine.
Tamoxifen is metabolized by the cytochrome P450 CYP 2D6 enzyme.
Poor CYP2D6 metabolizers are likely to experience impaired response to tamoxifen measured through mammographic density reduction.
Ultra rapid CYP2D6 metabolizers are risk for exaggerative response with pronounced adverse effects that may lead to treatment discontinuation with tamoxifen.