CYP2D6 Polymorphisms Research Articles

Cytochrome P-450 Polymorphisms and Clinical Outcome in Patients with Non-Small Cell Lung Cancer

Lung cancer is an increasing worldwide public health problem. Most patients with lung cancer have non-small cell lung cancer (NSCLC). These patients are mainly treated with standard platinum-based chemotherapy. Poor response and great inter-individual variety in treatment response occurs among these patients. There is accumulating evidence to support the hypothesis that genetic polymorphisms alter the drug response and survival. Cytochrome P450 (CYP) enzymes metabolize antineoplastic drugs and are involved in drug resistance. Polymorphic CYPs have altered enzyme activities and thus they may influence the response to chemotherapy and survival in patients with lung cancer. In the current review, recent findings with respect to the role of mainly CYP1A1, CYP1B1, CYP2D6, CYP2E1 and CYP3A4 gene polymorphisms in response to chemotherapy and survival in patients with NSCLC have been provided, which could be useful for clinicians in the prognosis of these patients who are mainly treated with platinum-based chemotherapy.

The Association of ADRB1 and CYP2D6 Polymorphisms With Antihypertensive Effects and Analysis of Their Contribution to Hypertension Risk

BackgroundGenetic factors have a vital influence on the pathogenesis of hypertension. In this retrospective study, we aimed to evaluate the association of ADRB1 and CYP2D6 polymorphisms with antihypertensive effects and perform an analysis of their contribution to hypertension risk. MethodsA total of 261 healthy individuals and 261 essential hypertension patients treated with metoprolol for 12 weeks were enrolled. ADRB1 and CYP2D6 genotypes were identified by xTAG liquid chip technology. We used multivariate logistic regression and a generalized linear mixed model to assess hypertension-related risk factors. ResultsThe allele frequencies of ADRB1 and CYP2D6 variants were 59.8% and 64.6% in the essential hypertension group and 70.3% and 65.9% in the controls, respectively. The genotype and allele distribution of ADRB1 were significantly different between the 2 groups (P < 0.05), but there was no significant difference in CYP2D6 distribution (P = 0.91 and 0.88). By logistic regression analysis, high fasting plasma glucose, smoking, high triglyceride and the Gly/Gly polymorphism in Arg389Gly ADRB1 all emerged as independent risk factors for hypertension. Additionally, the ADRB1 genotype played a major role in the antihypertensive effect of metoprolol and the patients with the Gly389Gly genotype showed a significantly better response to metoprolol than did those with a heterozygous ADRB1 mutation (Arg389Gly) (P = 0.027). ConclusionsThe results demonstrate that Gly/Gly polymorphism in Arg389Gly ADRB1 was an independent risk factor together with high fasting plasma glucose, smoking and high triglyceride; moreover, the patients who carried the Gly389Gly genotype had a significantly improved metoprolol antihypertensive effect than those with ADRB1.

Full-gene haplotypes refine CYP2D6 metabolizer phenotype inferences.

CYP2D6 is a critical pharmacogenetic target, and polymorphisms in the gene region are commonly used to infer enzyme activity score and predict resulting metabolizer phenotype: poor, intermediate, extensive/normal, or ultrarapid which can be useful in determining cause and/or manner of death in some autopsies. Current genotyping approaches are incapable of identifying novel and/or rare variants, so CYP2D6 star allele definitions are limited to polymorphisms known a priori. While useful for most predictions, recent studies using massively parallel sequencing data have identified additional polymorphisms in CYP2D6 that are predicted to alter enzyme function but are not considered in current star allele nomenclature. The 1000 Genomes Project data were used to produce full-gene haplotypes, describe their distribution in super-populations, and predict enzyme activity scores. Full-gene haplotypes generated lower activity scores than current approaches due to inclusion of additional damaging polymorphisms in the star allele. These findings are critical for clinical implementation of metabolizer phenotype prediction because a fraction of the population may be incorrectly considered normal metabolizers but actually may be poor or intermediate metabolizers.

The Prevalence of CYP2D6 Gene Polymorphisms among Filipinos and their use as Biomarkers for Lung Cancer Risk

Objectives. The highly polymorphic nature of the CYP2D6 gene and its central role in the metabolism of commonly used drugs make it an ideal candidate for pharmacogenetic screening. This study aims to determine the prevalence of CYP2D6 polymorphisms among Filipinos and their association to lung cancer. Method. Forty seven single nucleotide polymorphisms (SNPs) of the CYP2D6 gene were genotyped from DNA samples of 115 cases with lung cancer and age- and sex-matched 115 controls. Results. Results show that 18 out of 47 polymorphisms have significant genotypic variability (&gt;1% for at least 2 genotypes). No variant is associated with lung cancer. However, rs1135840, rs16947 and rs28360521, were found to be highly variable among Filipinos. Conclusion. This study demonstrated that CYP2D6 polymorphisms are present among Filipinos, which, although not found to be associated with lung cancer, can be useful biomarkers for future pharmacogenetic studies. The SNP rs16947 is found to be associated with cancer and timolol-induced bradycardia; the SNP rs1135840, on the other hand, is only shown to be linked with cancer. The genetic variant rs28360521 is known to be associated with low-dose aspirin-induced lower gastrointestinal bleeding.

Questions posées au Docteur Esther Decazes à propos de psychodynamique du travail et douleur chronique

According to various data, 25–50% of all patients with schizophrenia suffer from treatment resistance. It is believed that patients with treatment-resistant schizophrenia (TRS) have reduced cognitive skills, compared to the patients with a more favourable type of schizophrenia. However, according to some authors, there is limited evidence-based research on this topic at present.The total number of patients included 130 patients with a diagnosis of schizophrenia (F20 according to ICD 10). All patients were examined according to the following scales: Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Brief Assessment of Cognition in Schizophrenia (BACS).Our results showed that patients with TRS as a whole had worse cognitive functions than nTRS patients (p = 0.357). In the group of patients with TRS, polymorphism CYP2D6*4 showed an effect on executive functions. Carriers of the heterozygous GA genotype had higher values of executive functions (p = 0.043). No association between the studied gene polymorphic variants and TRS was found in this research.The polymorphic variant CYP2D6*4 showed an effect on cognitive function in the TRS group, regardless of their mental state and the effect of pharmacotherapy. In the future, it will be necessary to conduct larger prospective studies with a greater number of patients and a greater number of polymorphic variants of genes. Further identification of genetic predictors of cognitive impairment will improve researchers’ understanding of their causes and possibly move closer to more targeted therapy for schizophrenia.

Genetic Testing for CYP-2D6 Polymorphism Prior to Selective Serotonin Reuptake Inhibitor Prescribing: Results from a Decision Analysis Model

Genetic Testing for CYP-2D6 Polymorphism Prior to Selective Serotonin Reuptake Inhibitor Prescribing: Results from a Decision Analysis Model

Impact of CYP2D6 polymorphisms on endoxifen concentrations and breast cancer outcomes.

We investigated the impact of germline CYP2D6 genotyping done using the non-tumor specimen on endoxifen concentrations and/or clinical outcomes in breast cancer (BC) patients treated with tamoxifen in published studies. We evaluated published data from 13 001 patients in 29 studies. Mean±s.d. endoxifen concentrations were significantly lower in poor metabolizers (PM) versus extensive metabolizers (EM) (8.8±7.2 versus 22.3±11.8 ng ml-1; P<0.05). The PM status did not influence clinical outcomes in majority of the studies. However, only one study followed the Gaedigk activity scoring for phenotypic assignments, which predicted recurrence-free survival in CYP2D6 poor metabolizers. In two independent studies with 1676 patients, low endoxifen concentrations predicted poor BC-free survival. From our review of published data we found that standardization of CYP2D6 genotype-phenotype classification is needed in order to ensure effective evaluation of associations between CYP2D6 polymorphisms and endoxifen concentrations and BC outcomes. Universal implementation of this standardization classification system should be a priority among researchers and laboratories. Furthermore, additional clinical research is warranted to determine whether patients with CYP2D6 PM phenotypes or low endoxifen levels will have better clinical outcomes with increased tamoxifen dosing compared to standard dosing.

CYP2D6 genotype is not associated with survival in breast cancer patients treated with tamoxifen: results from a population-based study.

A number of studies have tested the hypothesis that breast cancer patients with low-activity CYP2D6 genotypes achieve inferior benefit from tamoxifen treatment, putatively due to lack of metabolic activation to endoxifen. Studies have provided conflicting data, and meta-analyses suggest a small but significant increase in cancer recurrence, necessitating additional studies to allow for accurate effect assessment. We conducted a retrospective pharmacogenomic analysis of a prospectively collected community-based cohort of patients with estrogen receptor-positive breast cancer to test for associations between low-activity CYP2D6 genotype and disease outcome in 500 patients treated with adjuvant tamoxifen monotherapy and 500 who did not receive any systemic adjuvant therapy. Tumor-derived DNA was genotyped for common, functionally consequential CYP2D6 polymorphisms (*2, *3, *4, *6, *10, *41, and copy number variants) and assigned a CYP2D6 activity score (AS) ranging from none (0) to full (2). Patients with poor metabolizer (AS=0) phenotype were compared to patients with AS>0 and in secondary analyses AS was analyzed quantitatively. Clinical outcome of interest was recurrence free survival (RFS) and analyses using long-rank test were adjusted for relevant clinical covariates (nodal status, tumor size, etc.). CYP2D6 AS was not associated with RFS in tamoxifen treated patients in univariate analyses (p>0.2). In adjusted analyses, increasing AS was associated with inferior RFS (Hazard ratio 1.43, 95% confidence interval 1.00-2.04, p=0.05). In patients that did not receive tamoxifen treatment, increasing CYP2D6 AS, and AS>0, were associated with superior RFS (each p=0.0015). This population-based study does not support the hypothesis that patients with diminished CYP2D6 activity achieve inferior tamoxifen benefit. These contradictory findings suggest that the association between CYP2D6 genotype and tamoxifen treatment efficacy is null or near null, and unlikely to be useful in clinical practice.

The predictive value of ABCB1, ABCG2, CYP3A4/5 and CYP2D6 polymorphisms for risperidone and aripiprazole plasma concentrations and the occurrence of adverse drug reactions.

We investigated in ninety Caucasian pediatric patients the impact of the main polymorphisms occurring in CYP3A, CYP2D6, ABCB1 and ABCG2 genes on second-generation antipsychotics plasma concentrations, and their association with the occurrence of adverse drug reactions. Patients with the CA/AA ABCG2 genotype had a statistically significant lower risperidone plasma concentration/dose ratio (Ct/ds) (P-value: 0.007) and an higher estimated marginal probability of developing metabolism and nutrition disorders as compared to the ABCG2 c.421 non-CA/AA genotypes (P-value: 0.008). Multivariate analysis revealed that the ABCG2 c.421 CA/AA genotype was found associated to a higher hazard (P-value: 0.004) of developing adverse drug reactions classified as metabolism and nutrition disorders. The ABCB1 2677TT/3435TT genotype had a statistically significant lower aripiprazole Ct/ds if compared with patients with others ABCB1 genotypes (P-value: 0.026). Information obtained on ABCB1 and ABCG2 gene variants may result useful to tailor treatments with these drugs in Caucasian pediatric patients.

Abstract 5033: Optimized CYP2D6 phenotype assignment for plasma endoxifen prediction in breast cancer patients treated with tamoxifen

Abstract Tamoxifen (Tam), a standard therapy for estrogen receptor (ER)-positive breast cancer, is bioactivated to its active metabolite endoxifen by the cytochrome P450 enzyme CYP2D6. CYP2D6 polymorphisms constituting extensive (EM), intermediate (IM) and poor (PM) metabolizer phenotypes are main determinants of variable endoxifen plasma concentrations and supposed to influence therapeutic efficacy. Genotype-guided prediction of TAM metabolizer status has long been debated to be useful for clinical dose adjustment in patients with impaired metabolism. As this requires accurate genotype-phenotype assignments, we tested several CYP2D6 phenotype classifications including the codeine metabolism-based scoring implemented by the ‘Clinical Pharmacogenetics Implementation Consortium’ (Crews et al. 2014, CPT) for their predictive value of active metabolite concentrations. We applied linear modelling of square-root transformed plasma endoxifen or log-transformed metabolic ratio (MR) endoxifen/desmethyl-TAM depending on CYP2D6 phenotype classification in a cohort of 936 pre- and postmenopausal TAM treated breast cancer patients of European, Middle Eastern Arabic, and Asian descent (Muerdter et al CPT 2011; Saladores et al. TPJ 2015). CYP2D6 diplotypes were defined by PM (*3, *4, *5, *6, *7), IM (*9, *10, *41), EM (*1, *2, *35) or UM (duplicated EM) alleles. CYP2D6 phenotypes were defined by various diplotype groupings and an adapted activity score regarding the *10 allele. Models were adjusted for CYP2C9 and CYP3A5 genotypes, and robust coefficients of determination (R2) with 95% confidence intervals from 10.000 bootstrap replicates were calculated using R package lmrob. Our analyses indicate, that the commonly used codeine-based CYP2D6 phenotype assignment poorly predicts CYP2D6 mediated endoxifen formation. This is evident from a low predictability (&amp;lt;20%) for both metabolite endpoints particularly in Asians, most likely due to a misclassification of abundant IM/IM (*10) diplotypes as EM. Importantly, the active metabolite-to-precursor MR appears to be the endpoint that is more closely linked to CYP2D6 enzyme activity, as it explains up to 68-82% of MR variability. In contrast, absolute endoxifen concentrations were only modestly predictable (38-57%) by CYP2D6 diplotype or other phenotype groupings. Moreover, a reduced activity for the *10 compared to other IM alleles appears to improve endoxifen predictabilty by phenotype. Personalized TAM treatment decisions based on plasma endoxifen prediction should rely on TAM specific CYP2D6 genotype-guided phenotype assignments that quantitatively capture the allele-dosage effects and that include endoxifen-to-precursor MR as the endpoint most directly linked to CYP2D6. Citation Format: Werner Schroth, Stefan Winter, Michel Eichelbaum, Thomas Muerdter, Matthias Schwab, Hiltrud Brauch. Optimized CYP2D6 phenotype assignment for plasma endoxifen prediction in breast cancer patients treated with tamoxifen [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 5033. doi:10.1158/1538-7445.AM2017-5033

CYP2D6 and CYP2C19 genotyping in psychiatric patients on psychotropic medication in the former Dutch Antilles.

This study was aimed to asses the prevalence of CYP2D6 and CYP2C19 polymorphisms in psychiatric patients and in volunteers from Dutch caribbean origin. In total, 435 individuals were genotyped for CYP2D6 and CYP2C19. Of these, 269 were psychiatric patients on psychotropic medication, living in Curaçao and 166 were volunteers from the Dutch Caribbean population. No differences in prevalence of alleles were found. Although prevalence of alleles appeared to be very different from African and Caucasian populations, the distribution into predicted phenotypes shows an equal distribution as in Caucasians.

Influence of CYP2D6, CYP3A4, CYP3A5 and abcb1 Polymorphisms in Pharmacokinetics and Safety of Ariprazole in Healthy Volunteers

Influence of CYP2D6, CYP3A4, CYP3A5 and abcb1 Polymorphisms in Pharmacokinetics and Safety of Ariprazole in Healthy Volunteers

A meta-analysis of the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol .

To conduct a meta-analysis on the effect of CYP2D6 polymorphism on the pharmacokinetics and pharmacodynamics of metoprolol. A systematic review and meta-analysis of studies on the effect of CYP2D6 polymorphism on metoprolol pharmacokinetics and pharmacodynamics was performed by using the China national knowledge infrastructure (CNKI), database for Chinese technical periodicals (VIP), Wanfang, and PubMed databases up to the end of January 2015. Review Manager 5.3 (the coherence collaboration, www.gradepro.org) and comprehensive Meta-Analysis Software v2 (CMA) Biostat, Englewood, NJ, USA) were used for meta-analysis. A total of 567 cases from 7 studies were included in the present study. Meta-analysis results showed that the area under the curve (AUC)_0-∞ (RR=-6.75, 95% CI (-9.18, -4.31), p<0.00001); C_max (RR=-2.40, 95% CI (-3.25, -1.54), p<0.00001); T_1/2 (RR=-4.81, 95% CI (-6.86, -2.76), p<0.00001); CL/F (RR=1.60, 95% CI (1.03,2.17), p<0.00001); heart rate (RR=1.48, 95% CI (0.03, 2.92), p=0.05), systolic blood pressure (RR=-0.69, 95% CI (-1.85,0.47), p=0.24); and diastolic blood pressure (RR=-1.95, 95% CI (-3.14, -0.76), p=0.001). Begg's funnel plot test showed that the pharmacokinetic parameters (AUC_0-∞, C_max, T_1/2, and CL/F) and pharmacodynamic parameters (HR, DBP, and SBP) were symmetric. Egger's test showed that the pharmacokinetic parameters were asymmetrical, and its intercept was statistically significant (p < 0.05), which was indicative of publication bias. The pharmacodynamic parameter intercept was not statistically significant (p > 0.05), indicating that no publication bias existed. CYP2D6 polymorphism significantly influenced the pharmacokinetic parameters of metoprolol. It also affected heart rate and diastolic blood pressure, whereas systolic pressure was not affected. .

Influence of genetic variants of CYP2D6, CYP2C9, CYP2C19 and CYP3A4 on antiepileptic drug metabolism in pediatric patients with refractory epilepsy.

Identified the polymorphisms of CYP2D6, CYP2C9, CYP2C19 and CYP3A4, within a rigorously selected population of pediatric patients with drug-resistant epilepsy. The genomic DNA of 23 drug-resistant epilepsy patients and 7 patients with good responses were analyzed. Ten exons in these four genes were genotyped, and the drug concentrations in saliva and plasma were determined. The relevant SNPs with pharmacogenomics relations were CYP2D6*2 (rs16947) decreased your activity and CYP2D6*4 (rs1065852), CYP2C19*2 (rs4244285) and CYP3A4*1B (rs2740574) by association with poor metabolizer. The strongest risk factors were found in the AA genotype and allele of SNP rs3892097 from the CYP2D6 gene, followed by the alleles A and T of SNPs rs2740574 and rs2687116, respectively from CYP3A4. The most important concomitance was between homozygous genotype AA of rs3892097 and genotype AA of rs2740574 with 78.3% in drug-resistant epilepsy patients as compared to 14.3% in control patients. The results demonstrated the important role of the CYP 3A4*1B allelic variant as risk factor for developing drug resistance and CYP2D6, CYP2C19 SNPs and haplotypes may affect the response to antiepileptic drugs.

Inference of the Genetic Polymorphisms of CYP2D6 in Six Subtribes of the Malaysian Orang Asli from Whole-Genome Sequencing Data.

CYP2D6 is one of the major enzymes in the cytochrome P450 monooxygenase system. It metabolizes ∼25% of prescribed drugs and hence, the genetic diversity of a CYP2D6 gene has continued to be of great interest to the medical and pharmaceutical industries. This study was designed to perform a systematic analysis of the CYP2D6 gene in six subtribes of the Malaysian Orang Asli. Genomic DNAs were extracted from the blood samples followed by whole-genome sequencing. The reads were aligned to the reference human genome hg19 and variants in the CYP2D6 gene were analyzed. CYP2D6*5 and duplication of CYP2D6 were analyzed using previously established methods. A total of 72 single nucleotide polymorphisms were identified. CYP2D6*1, *2, *4, *5, *10,*41, and duplication of the gene were found in the Orang Asli, whereby CYP2D6*2 and *41 alleles are reported for the first time in the Malaysian population. The findings in this study provide insights into the genetic polymorphisms of CYP2D6 in the Orang Asli of Peninsular Malaysia.

CYP450 genotype and aggressive behavior on selective serotonin reuptake inhibitors.

Genetic variants for selective serotonin reuptake inhibitor (SSRI) metabolizing enzymes have been hypothesized to be a risk factor for aggression as adverse drug effect of SSRIs. Our aim was to assess the possible involvement of these polymorphisms on aggression when using SSRIs. A retrospective noninterventional case-control study was performed on 18 cases. The genetic profile of two main genes involved in the metabolism of SSRIs was determined, and predicted phenotype frequencies were compared with Dutch controls and literature data. Predicted CYP2C19 and CYP2D6 phenotypes for all SSRIs analyzed together did not show a significant difference between cases and controls. We found no supporting evidence for a significant relationship between CYP2C19 and CYP2D6 polymorphisms, and aggression in patients using SSRIs.

Should a routine genotyping of CYP2D6 and CYP2C19 genetic polymorphisms be recommended to predict venlafaxine efficacy in depressed patients treated in psychiatric settings?

The antidepressant venlafaxine (VEN) is metabolized by CYP2D6 and CYP2C19. The aim of this study was to assess the relevance of generalizing to daily practice the genotyping of CYP2D6 and CYP2C19 to predict VEN efficacy in depressed patients treated in psychiatric settings. This study was nested in a naturalistic cohort, with 206 patients requiring a new antidepressant treatment and genotyped for CYP2D6 *3, *4, *5 del, *6, *2xN, *10, *41 and CYP2C19 *2, *3, *4, *5, *17 alleles. CYP2D6 and CYP2C19 phenotypes were associated neither with the Hamilton depression rating scale score improvement, nor with response and remission. Routine CYP2D6 and CYP2C19 genotyping cannot be recommended to predict VEN efficacy in depressed patients treated in psychiatry settings.

Serum Clomipramine and Desmethylclomipramine Levels in a CYP2C19 and CYP2D6 Intermediate Metabolizer

Pharmacogenetics within psychiatry has the potential to aid in the dose and selection of medications. A substantial number of psychiatric medications are metabolized through either of the highly polymorphic drug-metabolizing enzymes CYP2D6 and CYP2C19. Of these, clomipramine is subject to metabolism by both CYP2C19 and CYP2D6, leaving individuals with deficiencies of these drug-metabolizing enzymes at risk of higher concentrations of the parent molecule. Herein, we present the case of a 29-year-old male with diagnoses of depression and obsessive compulsive disorder who had trialed and failed a dozen psychiatric medications, many of which are subject to metabolism by CYP2D6 and/or CYP2C19, and had most recently been taking clomipramine for approximately 2.5 years. Pharmacogenetic testing revealed this patient to be an intermediate metabolizer for both CYP2C19 (*1/*2) and CYP2D6 (*4/*41), which resulted in considerably elevated serum trough concentrations of clomipramine and its active metabolite desmethylclomipramine. This case provides a retrospective view of how the knowledge of an individual's pharmacogenetic test results can aid in their clinical care.

Clinical Pharmacogenetics Implementation Consortium (CPIC) guideline for CYP2D6 genotype and use of ondansetron and tropisetron.

5-hydroxytryptamine type 3 (5-HT3) receptor antagonists are used in the prevention of chemotherapy- induced, radiation-induced and postoperative nausea and vomiting. CYP2D6 polymorphisms can influence the metabolism of some of these drugs (i.e. ondansetron and tropisetron) thereby affecting drug efficacy. We summarize evidence from the published literature supporting these associations and provide therapeutic recommendations for ondansetron and tropisetron based on CYP2D6 genotype (updates at www.pharmgkb.org ).

CYP450 enzymes genetic polymorphism influence on treatment of affective disorders

IntroductionIndividualized treatment decisions in psychiatry may be important, since substantial part of first choice drugs are ineffective or cause side effects. Polymorphic variants of genes that code CYP450 enzymes cause differences in their activity and therefore in efficacy and safety of drugs that are metabolized by them.Aim of the studyDetermine whether pharmacogenetic testing of CYP2D6, CYP2C19 and CYP2C9 polymorphism would have had influence on selected patients’ treatment courses.MethodsFive patients that were diagnosed for treament-resistant mood disorders in Vilnius university hospital Santariskiu clinics centre of neurology, department of psychiatry were invited to give blood samples for genetic testing retrospectively. Patients’ CYP2C19, CYP2D6 and CYP2C9 enzymes genetic polymorphism results were compared with previous empirical pharmacological treatment courses of these patients.ResultsIn four out of five cases significant polymorphism of CYP2C19 enzyme allele was detected. In all of these cases 1*/2* variant, that conditions intermediate metabolizer phenotype, was identified. Alterations in CYP2D6 and CYP2C19 regions were not found. In three cases the presence of varied genetic variant could have been clinically relevant. In two of these cases Sertraline and valproates, that are both metabolized by CYP2C19 enzyme, were taken by patients and side effects were observed. Unsuccessful treatment was repeated without effect, both in clinical and outpatient environment. Continuous rehospitalization took place until appropriate empirical treatments were established.ConclusionsPharmacogenetic testing could have had influence on treatment choices for three out of five selected patients leading to less side effects and rehospitalizations.Disclosure of interestThe authors have not supplied their declaration of competing interest.