Table 2.
Testing techniques identified by Genetic Testing Registry (GTR) screening of the methodology category ‘Molecular Genetics’ for drugs listed as ‘Actionable PGx’ (EU) at PharmGKB
| Drug | Disease | Gene/Biomarker | Molecular genetics (GTR) |
|---|---|---|---|
| Amifampridine phosphate | Lambert-Eaton myasthenic syndrome | NAT2 | CNV detection NGS + qPCR SNP detection |
| Aripiprazole | Schizophrenia | CYP2D6 | RT-PCR, RT-qPCR, PCR with allele-specific hybridization+SNP detection (ASPE+Mass Spectrometry), CNV detection NGS + qPCR SNP detection, SNP detection |
| Brexpiprazole | Schizophrenia | CYP2D6 | CNV detection NGS + qPCR SNP detection |
| Brivaracetam | Epilepsy | CYP2C19 | CNV detection NGS + qPCR SNP detection, microarray |
| Clopidogrel | Secondary prevention of atherothrombotic events, prevention of atherothrombotic and thromboembolic events in atrial fibrillation | CYP2C19 | NGS/ MPS, RT-PCR, MLPA, SNP detection (real-time polymerase chain reaction (PCR) + Single Nucleotide Primer Extension), bidirectional Sanger sequence analysis, solid-phase electrochemical methodology, ASPE + mass spectrometry, PCR with allele-specific hybridization, RT-qPCR, multiplex ligation-dependent probe amplification (MLPA), quantitative PCR (qPCR), KASP genotyping, , quantitative PCR (qPCR), RT-qPCR |
| Darifenacin (hydrobromide) | Urge incontinence and/or increased urinary frequency and urgency as may occur in adult patients with overactive bladder syndrome | CYP2D6 | CNV detection NGS + qPCR SNP detection |
| Dolutegravir | HIV infection | UGT1A1 | CNV detection NGS + qPCR SNP detection |
| Duloxetine |
Treatment of major depressive disorder Treatment of diabetic peripheral neuropathic pain Treatment of generalised anxiety disorder |
CYP2D6 | SNP detection, RT-qPCR |
| Efavirenz | HIV infection | CYP2B6 | MLPA, NGS/ MPS, MLPA + bidirectional Sanger sequence analysis, bidirectional Sanger sequence analysis, CNV detection NGS + qPCR + SNP detection (NGS), NGS/MPS + bidirectional Sanger sequence analysis, SNP detection (real-time PCR, microarray analysis), qPCR, RT-qPCR, KASP genotyping |
| Efavirenz/emtricitabine/tenofovir disoproxil | HIV infection | CYP2B6 | MLPA, NGS/ MPS, MLPA + bidirectional Sanger sequence analysis, bidirectional Sanger sequence analysis, CNV detection NGS + qPCR SNP detection, NGS/MPS + bidirectional Sanger sequence analysis, SNP detection (real-time PCR, microarray analysis), qPCR, RT-qPCR, KASP genotyping |
| Ethinyl estradiol/norelgestromin | Female contraception | Predisposition for venous thromboembolism (including F5), antithrombin-III deficiency (SERPINC1), protein C deficiency (PROC) and protein S deficiency (PROS)) | Microarray |
| Fesoterodine | Treatment of the symptoms that may occur with overactive bladder syndrome | CYP2D6 (poor metabolism) | CNV NGS + qPCR SNP detection |
| Gefitinib | Advanced or metastatic non-small-cell lung cancer | CYP2D6 (poor metabolism) | CNV NGS + qPCR SNP detection, SNP detection, RT-qPCR |
| Glibenclamide | Neonatal diabetes mellitus | G6PD (deficiency) | SNP detection |
| Glimepiride | Type 2 diabetes mellitus | G6PD (deficiency) | SNP detection, microarray |
| Irinotecan | Metastatic adenocarcinoma of the pancreas | Homozygozity for UGT1A1*28 allele | PCR electrophoresis, capillary gel, PCR, fragment analysis, bidirectional Sanger sequence analysis, PCR with allele-specific hybridization, PCR capillary gel electrophoresis |
| Lapatinib | Breast cancer, in which tumours overexpress HER2 (ErbB2) | HLA-DQA1*02:01 and HLA-DRB1*07:01 | Microarray |
| Lesinurad | Hyperuricaemia in gout patients | CYP2C9 (poor metabolism) | Microarray, ASPE + mass Spectrometry |
| Mercaptopurine | Acute lymphoblastic leukaemia (ALL) | TPMT, NUDT15 | RT-qPCR, RT-PCR with gel analysis, Microarray, CNV detection NGS quantitative PCR (qPCR) SNP detection, PCR |
| Pazopanib | Advanced renal cell carcinoma | HLA-B | CNV detection NGS + qPCR SNP detection |
| Rasburicase | Acute hyperuricaemia | G6PD | Microarray (D,T), NGS/MPS |
| Vortioxetine | Major depressive episodes | CYP2D6 | CNV Detection NGS + qPCR SNP Detection |
The overview does not privide a sufficient profile of suitable testing techniques for decision support in clinical diagnostics and therapy management in Europe as regulatory clearances, clinical utility, and analytical and clinical validity were not assessed in the evaluations for this review article
ASPE allele-specific primer extension, CNVs copy number variations, CYP cytochrome P450, F5 factor 5, G6PD glucose-6-phosphate dehydrogenase, HLA-B*5701 human leukocyte antigen B*5701, HLA-DQA1 major histocompatibility complex, class II, DQ alpha 1, HSD3B7 3β-hydroxy-Δ5-C27-steroid oxidoreductase, KASP competitive allele specific PCR, MLPA Multiplex Ligation-dependent Probe Amplification, MPS massively parallel sequencing, NAT2 N-acetyltransferase 2, NGS next-generation sequencing, NUDT15 nudix hydrolase 15, PCR polymerase chain reaction, PROC Protein C, PROS Protein S, qPCR quantitative real-time PCR, RT-PCR reverse transcriptase PCR, SERPINC1 serpin family C member 1, SNPs single nucleotide polymorphysms, TPMT thiopurine S-methyltransferase, UGT1A1 uridine diphosphate glucuronosyltransferase 1A1