Pharmacogene: CYP2D6

Type of pharmacogene: Pharmacokinetic

CYP2D6 codes for the drug-metabolizing enzyme CYP2D6. This enzyme is responsible for metabolizing approximately twelve percent (19%) of medications. Variants of this pharmacogene may affect drug metabolism of substrate drugs.

Pharmacogene Variant of the Week (PVOW 2_15_2018): CYP2D6*9

Reference single nucleotide polymorphism number: rs5030656 

DNA base change: del CTT 

Pharmacogene function as compared to normal function: Decreased function

Pharmacogene product: CYP2D6 drug metabolizing enzyme

Pharmacogene product activity as compared to normal activity: Decreased

General Conceptual Pharmacogene Variant Information

CYP2D6*9 Imparts:

Increased drug exposure

- Higher maximum concentration

- Increased area under the curve (AUC)

- Longer half-life

Note: For a prodrug, less of the active drug will be formed.

Drug Exposure Plot
 

Note: "No" or "decreased" function/activity shown in relative terms.

Conceptual statement 1: Notwithstanding other variables, individuals with one (heterozygous) or two (homozygous) copies of this pharmacogene variant will likely have decreased drug metabolism of an administered active drug, with increased exposure and potential increased risk of an adverse drug reaction.

Conceptual statement 2: Notwithstanding other variables, individuals with one (heterozygous) or two (homozygous) copies of this pharmacogene variant will likely have decreased drug metabolism of an administered prodrug, with decreased exposure to the active drug and potential increased risk of drug inefficacy.

The reader is directed to https://www.pharmgkb.org/haplotype/PA165948317