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Table 9 Genotype-phenotype drug response interpretations of the Pharmacogenomics Advisory Group-approved drug-gene pairs simvastatin and SLCO1B1 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 an cestry

East Asian ancestry

SLCO1B1*1/*1

64

92

79

Normal drug transport

Normal response and risk of adverse drug reactions to simvastatin

80 mg simvastatin maximum dose

SLCO1B1*1/V174A, SLCO1B1*1/*6, and another rare diplotype, SLCO1B1*1/*3

32

8

20

Intermediate decreased drug transport

Intermediate increase in risk of myopathy from simvastatin

40 mg simvastatin maximum dose

SLCO1B1 V174A/V174A, SLCO1B1*6/V174A, and other rare diplotypes (see Additional file 1: Table S28)

4

<1

1

Decreased drug transport

Increased risk of myopathy from simvastatin

20 mg simvastatin maximum dose

  1. Abbreviations: FDA Food and Drugs Administration, PD pharmacodynamic, PK pharmacokinetic.
  2. aSupporting evidence may be found in Additional file 2: Section S7.0 to 7.7 and Additional file 1: Tables S26 to S28. 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 S28). 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 S27) and Hardy-Weinberg principles.