Significance of CYP2D Polymorphism

Cytochrome P450 (CYP450) is a superfamily of metabolizing enzymes which play a major role in the biotransformation of xenobiotics, i.e. drug, foods,, chemicals, pollutants, and endogenous compounds. The activity of CYP450 is one of the most influent factors on the drug-pharmacokinetics. CYP2D6 is one of CYP450 isoforms which takes responsibility in the metabolism of varieties clinically used drugs that usually have narrow therapeutic index such as antidepressants and anti-hypertensives. The activity of CYP2D6 is affected by both exogenous and endogenous influences, including genetic variation, epigenetic variation, and concurrently used drugs. Genetic variation of CYP2D6 genes is either hereditary or acquired mutation. The variation of CYP2D6 activity due to genetic mutation is referred to polymorphism. Polymorphism of CYP2D6 has been reported to associate with failure of pharmacotherapy and risk of adverse effects. Small rodents are often employed for the pharmacokinetic study by using the human orthologue as the determinant, however, the difference of human CYP2D6 and small rodent Cyp2d are remarkable. Hence, this review focuses on significance of human CYP2D6 , its rodent human orthologue, CYP2D6 genetic variation and polymorphism, and some clinical impacts of CYP2D6 polymorphism.