Skip to main content

Table 3 Genotype-phenotype drug response interpretations of the Pharmacogenomics Advisory Group-approved drug-gene pair clopidogrel and CYP2C19 a

From: The Coriell personalized medicine collaborative pharmacogenomics appraisal, evidence scoring and interpretation system

Common diplotypesb

Expected population frequency, %c

PK/PD phenotype

Clinical phenotype

FDA guidelines

Caucasian ancestry

African ancestry

East Asian ancestry

CYP2C19*1/*1

38

36

35.5

EM: normal enzymatic function and normal drug activation; normal platelet inhibition

Likely to have a normal response to standard dose of clopidogrel

–

CYP2C19*1/*2, CYP2C19*1/*8, and other rare diplotypes (see Additional file 1: Table S4)

19

22

46

IM: reduced enzymatic function resulting in reduced drug activation; decreased platelet inhibition

Increased risk of ischemic event while on clopidogrel.d Should use alternative anti-platelet medication

–

CYP2C19*2/*2 and other rare diplotypes (see Additional file 1: Table S4)

2

3

15

PM: greatly reduced or abolished enzymatic function, leading to little or no drug activation; greatly diminished platelet inhibition

Increased risk of ischemic event while on clopidogrel.d Should use alternative anti-platelet medication

CYP2C19 PMs with ACS or undergoing PCI treated with Plavix at recommended doses exhibit higher cardiovascular event rates than do patients with normal CYP2C19 function. Consider alternative treatment or treatment strategies in patients identified as CYP2C19 PMs

CYP2C19*1/*17, CYP2C19*17/*17

34

31

2

UM: enhanced enzymatic function leading to greater drug activation

Possible increased risk of bleeding; but also likely to derive greater protection from ischemic event while on clopidogrel

–

CYP2C19*2/*1 7 and other rare diplotypes (see Additional file 1: Table S4)

7

8

1.5

Unk: metabolizer status undetermined and therefore unknown. PD data indicates platelet response is intermediate between likely IMs and EMs

Unknown effect on drug response

–

  1. Abbreviations: ACS acute coronary syndromes, EM Extensive metabolizer, FDA Food and Drugs Administration, IM intermediate metabolizer, PCI percutaneous coronary intervention, PD pharmacodynamic, PK pharmacokinetic, PM poor metabolizer, UM Ultra-rapid metabolizer, Unk metabolizer status unknown.
  2. aSupporting evidence may be found in Additional file 2: Section S1.0-1.7, and Additional file 1:Tables S2-S4. These include summaries of the PhAESIS evaluation and referenced publications supporting the drug-gene clinical phenotypes.
  3. bDiplotypes with frequencies of less than 0.4% in Caucasians are included above. Other rare diplotypes that fall under the same phenotype category can be found in the genotype-phenotype Punnett table (see Additional file 1: Table S4). Diplotypes above and in the genotype-phenotype Punnett table include both clinically validated genetic results (those that include variants with evidence code 1) and results that include variants with evidence scores 2 to 7 (potentially clinically relevant). The latter require further validation to support their inclusion for clinical reporting.
  4. cPopulation frequencies are estimated based on reported gene variant allele frequencies (see Additional file 1: Table S3) and Hardy-Weinberg principles.
  5. dGreater risk of ischemic event in patients with ACS undergoing PCI.
Back to article page

Genome Medicine

ISSN: 1756-994X

Contact us