3.2 Pharmacogenetic variants and their clinical relevance for
current medication
Phenotypes of the 16 tested genes were derived from the identified PGx
variants, and their frequencies in the study population are presented inFigure 2 . Table 2 presents an overview of the tested
genes, drugs that are affected by these variants along with their
corresponding PHARMGKB classification, as well as the frequency of these
variants in our study population. A detailed listing of drug-gene pairs
and their classification of clinical relevance according to PHARMGKB is
presented in Table S2 .
The 16-gene PGx panel detected genetic variants, i.e. non wildtype
genes, in 3.7 % (for DPYD) to 78.5 % (for ABCB1) of all patients.
CYP2D6, CYP2C19, CYP2C9 and TPMT variants are of particular interest
because they relate to drugs where PGx testing is classified as required
or recommended. Phenotype variants were detected for CYP2D6 in 50%,
CYP2C19 in 52%, CYP2C9 in 34% and TPMT in 5.9% of the study
population. Of note, Table 2 provides the numbers and proportions of all
patients with non-wildtype variants, but not all variants necessarily
have the same classification for all listed drugs. E.g. the number of
subjects with CYP2C19 variants in Table 2 refers to IM, PM as well as to
EM phenotypes, but for clopidogrel only the IM and PM phenotypes are
“actionable”.
Therefore, Table 3 presents a detailed analysis for each drug
that triggered PGx-testing including the number of patients with related
genetic variants. The additional columns present an analysis of the
clinical relevance of those variants. First, we present the number of
patients where SONOGEN XP recommends to consider a change of the drug
that triggered PGx testing. Second, we present the number of patients
where the subsequent clinical pharmacology expert evaluation recommended
a change of that trigger drug. Third, we present the number of patients
where the 16-gene PGx panel identified additional drug-gene variant
interactions in their current comedication.
Overall, among 102 patients with a drug-specific indication for PGx
testing, actionable variants for the triggering drugs were identified in
36 patients (35.3%) according to SONOGEN XP, and after clinical expert
evaluation including further patient-specific factors recommendations to
change PGx-triggering drugs were actually issued in 33 patients (32.4
%). The majority of these recommendations (19 patients) referred to
current therapy with clopidogrel.
Furthermore, the 16-gene PGx panel identified genetic variants that
related to the current comedication and led to “coincident” additional
clinical recommendations to adjust comedication in 23 out of 102
patients (22.5%) with a drug-specific indication for PGx testing, and
in 3 out of 33 patients (9.1%) with a screening indication.