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Polymorphisms

Two isoforms of cytochrome P450, CYP2D6 and CYP2C19, are known to be subject to genetic variation in the gene that codes for the enzyme in certain populations of humans. These are referred to as polymorphisms. A variation in the gene that codes for these enzymes results in variants that produce responses ranging from non-functional to higher than normal activity.
CYP polymorphisms responsible for poor metabolism are the result of either the synthesis of an unstable or inactive enzyme or a genetic mutation that blocks the synthesis of the enzyme. On the other end of the spectrum, it is possible for a gene to be duplicated, leading to increased activity of the enzyme.
Poor metabolizers
  • Have inherited a non-functional gene from each parent.
  • Have no CYP2D6 or no CYP2C19 activity.
  • 5-10% of Caucasians are thought to be poor CYP2D6 metabolizers.
  • 2-5% of African Americans are thought to be CYPD26 poor metabolizers.
  • 1% of Asians are thought to be CYPD26 poor metabolizers.
  • 20% of Asians are thought to be CYP2C19 poor metabolizers.
Intermediate metabolizers
  • Have inherited a non-functional gene from one parent and a normal gene from the other parent.
  • Have less than normal CYP2D6 or CYP2C19 activity.
Extensive metabolizers
  • Have inherited a normal gene from each parent.
  • Have normal CYP2D6 or CYP2C19 activity.
  • Found in majority of all populations.
Ultrarapid metabolizers
  • Have inherited a normal gene from one parent and a gene that expresses amplified activity from the other parent.
  • Have higher than normal CYP2D6 or CYP2C19 activity.
  • 20% of Greeks are thought to be CYP2D6 ultrarapid metabolizers.
  • 20% of Saudis are thought to be CYP2D6 ultrarapid metabolizers.
  • 30% of Ethiopians are thought to be CYP2D6 ultrarapid metabolizers.