Pharmacogenomics最新文献

Objective: This study aimed to estimate the clinical utility of performing multi-gene pharmacogenetic testing on patients undergoing gynecologic surgery/procedure by evaluating the prescribing rate of Clinical Pharmacogenetics Implementation Consortium (CPIC) level A medications and frequency of drug-gene interactions (DGIs).

Methods: The electronic health record was queried for 76 current procedural terminology codes to identify gynecologic surgeries/procedures that occurred between 1 January 2015 to 31 December 2020 in patients with at least one of 152 international classification of disease codes. Prescription data for CPIC level A medications was extracted. Those enrolled in the Penn Medicine Biobank were assessed for DGIs.

Results: The cohort consisted of 7798 female patients and 682 were in the biobank. Up to 6 years following their surgery or procedure, 80% were ordered ≥1 CPIC level A medication. Over half (54%) of these medications were ordered within 3 days after their surgery or procedure. The most common CPIC level A medications ordered were ibuprofen (57%) and ondansetron (42%). Overall, 7% of the cohort had ≥1 known or predicted DGI with medications they were prescribed.

Conclusion: Multi-gene pharmacogenetic testing may be beneficial to gynecologic surgery/procedure patients by assisting clinicians with prescribing postoperative analgesics and future medications.

Acute generalized exanthematous pustulosis (AGEP) is a rare drug reaction characterized by numerous pustules on an erythematous base. In some cases, hydroxychloroquine (HCQ) can cause AGEP. There is an association between HLA genes and AGEP according to pharmacogenomic studies. In this case report, we present the case of a 36-year-old female who developed HCQ-induced AGEP with HLA-typing. According to our findings, the patient had HLA-B 58:01, HLA-C 08:01, and HLA-A 02:06. A pharmacoeconomic perspective of HLA genotyping before drug prescription is shown in this result.

Aim: This study evaluated associations between CYP3A4*22 and variants in other pharmacogenes (CYP3A5, SULT2A1, ABCB1, ABCG2, ERCC1) and the risk for palbociclib-associated toxicities.Materials & methods: Two hundred cancer patients who received standard-of-care palbociclib were genotyped and associations with toxicity were evaluated retrospectively.Results: No significant associations were found for CYP3A4*22, CYP3A5*3, ABCB1_rs1045642, ABCG2_rs2231142, ERCC1_rs3212986 and ERCC1_rs11615. Homozygous variant carriers of SULT2A1_rs182420 had higher incidence of dose modifications due to palbociclib toxicity (odds ratio [OR]: 4.334, 95% CI: 1.057-17.767, p = 0.042). ABCG2_rs2231137 variant carriers had borderline higher incidence of grade 3-4 neutropenia (OR: 4.14, 95% CI: 0.99-17.37, p = 0.052).Conclusion: Once validated, SULT2A1 and ABCG2 variants may be useful to individualize palbociclib dosing to minimize toxicities and improve treatment outcomes.

Aim: Clopidogrel requires CYP2C19 activation to have antiplatelet effects. Pharmacogenetic testing to identify patients with impaired CYP2C19 function can be coupled with clinical decision support (CDS) alerts to guide antiplatelet prescribing. We evaluated the impact of alerts on clopidogrel prescribing.Materials & methods: We retrospectively analyzed data for 866 patients in which CYP2C19-clopidogrel CDS was deployed at a single healthcare system during 2015-2023.Results: Analyses included 2,288 alerts. CDS acceptance rates increased from 24% in 2015 to 63% in 2023 (p < 0.05). Adjusted analyses also showed higher acceptance rates when clopidogrel had been ordered for a percutaneous intervention (OR: 28.7, p < 0.001) and when cardiologists responded to alerts (OR: 2.11, p = 0.001).Conclusion: CDS for CYP2C19-clopidogrel was effective in reducing potential drug-gene interactions. Its influence varied by clinician specialty and medication indications.

In 2021, the Clinical Pharmacology Department of Hospital Universitario de La Princesa launched the PriME-PGx initiative (Multidisciplinary Initiative of the Hospital Universitario de La Princesa for the Implementation of Pharmacogenetics) to promote the expansion of pharmacogenetics in hospitalized patients. We establish seven pharmacogenetic profiles based on the specific needs of seven departments: Oncology, Pain Unit, Neuropsychiatry, Internal or Infectious Medicine, Cardiology, Gastroenterology and Immunosuppressants. The experience of the last 3 years reflects a total of 1421 reports (37.4% being oncology profiles), with a gradual increase in the number of requests each year. With this project, we aim to expand the availability and utility of pharmacogenetic biomarkers to achieve personalised therapy that avoids adverse drug reactions and therapeutic failure.

Pharmacogenomics (PGx) is a practice that investigates the link between genetic differences and drug response in patients. This can improve treatment effectiveness and reduce harmful side effects. However, has yet to be adequately realized in developing nations. Three surveys were conducted between November 2022 to March 2023 in Egypt and Lebanon. The first survey assessed availability of PGx testing in different healthcare facilities; the second one assessed knowledge, interest and attitude toward learning about PGx among pharmacists and physicians; and the third one assessed interest in providing PGx education at academic levels. In Egypt, a few of the surveyed healthcare facilities are conducting some form of pharmacogenetic testing. In Lebanon, very few germline pharmacogenomic tests are offered in Greater Beirut's leading hospitals, and no other testing was recorded. PGx education attracts considerable interest, with 34.3% of pharmacists very interested and 48.8% interested. Similarly, 24.8% of total physicians were very interested while 44.8% were interested. Academic professionals in the surveyed institutions in both countries agreed on the need for educational programs in PGx and 78.2% agreed that there were good opportunities for implementing PGx testing. These findings clearly indicate the need to develop and implement educational programs in PGx in the Middle-East.

Aim: To evaluate the feasibility and impact of using CYP2C19 genotype to guide selection of antiplatelet therapy in patients undergoing intracranial aneurysm treatment with a flow diversion stent in a real-world clinical setting.Patients & methods: A single-center, retrospective, observational cohort study was conducted in 112 patients undergoing intracranial aneurysm repair with flow-diversion stenting from 2014 to 2021. Data were abstracted from health records. The frequency of clopidogrel or alternative therapy (ticagrelor or prasugrel) use was compared across CYP2C19 status (intermediate or poor metabolizer [IM/PM] vs. normal, rapid, or ultrarapid metabolizer [NM/RM/UM]).Results: In the study population, CYP2C19 genotype testing was performed on 110 (98.2%) patients; of these, 106 (97.2%) had results available prior to the stent procedure and 28 (25.5%) were IM/PMs. Alternative therapy was used more frequently in IM/PMs compared with NM/RM/UMs (57.1 vs. 8.5%, respectively, p < 0.0001). The frequency of thromboembolic events over 12 months did not significantly differ across clopidogrel-treated IM/PMs, clopidogrel-treated NM/RM/UMs and patients on alternative therapy (p = 0.352); although, event numbers were low.Conclusion: A pre-emptive CYP2C19 genotyping strategy to guide antiplatelet therapy selection in intracranial aneurysm repair patients is feasible in a real-world clinical setting. Larger studies are needed to assess the impact on clinical outcomes.

Aim: Implementation of CYP2C19 point-of-care (POC) pharmacogenetic (PGx) testing with personalized treatment recommendations. Methods: POC CYP2C19 genotyping plus expert evaluation of risk factors for ischemic and bleeding events. Results: 167 patients underwent PGx testing, 54 (32.3%) were CYP2C19 loss of function carriers, and POC versus standard PGx analysis results for *2 and *3 variants matched in 100%. Antiplatelet therapy was adjusted in 44 patients (26.3%), but always required consideration of patient-specific factors. Conclusion: CYP2C19 POC-PGx is reliable and offers clinically relevant advantages for immediate evidence-based adaptations of antiplatelet therapy, whereas in less acute cases conventional PGx testing can also have advantages. Antiplatelet therapy has become more complex, and implementation of PGx-based personalized antiplatelet therapy requires complementary expert knowledge.

Purpose: To compare minor allele frequencies (MAFs) of psychiatric drug response variants in a Brazilian admixed cohort with global populations and other Brazilian groups. Methods: PharmGKB MAFs were gathered from publicly available genetic datasets for Brazil and worldwide. Results: Among 146 variants in CYP2D6 and CYP2C19, 41 were present in Brazil, mostly rare (MAF <1%). 11 variants showed significant MAF differences with large effect sizes compared with global populations. CYP2C19*3 (rs4986893), CYP2C19*17 (rs12248560), CYP2D6*17 (rs28371706-A) and CYP2D6*29 (rs61736512) exhibited higher frequencies in Brazil, with the latter three also differing from other Brazilian groups. Conclusion: This study highlights significant pharmacogenomic diversity in Brazil and globally, underscoring the need for more research in personalized psychiatric drug therapy.

Background: Previous differences in guideline recommendation strength for CYP2C19 intermediate metabolizers may have limited genotype (PGx)-optimal post-percutaneous coronary intervention antiplatelet prescribing.Results: In this single-center retrospective observational cohort study of CYP2C19 intermediate metabolizers, patients prescribed PGx-optimal therapy were younger and less likely on anticoagulation (2 vs 12%; p = 0.006). More patients prescribed PGx-optimal therapy possessed commercial insurance (36 vs 7%; p < 0.001), which was a predictor for PGx-optimal selection (OR: 6.464; 95% CI: 2.386-17.516; p < 0.001).Conclusion: Anticoagulation use was significantly associated with clopidogrel use (OR: 0.138; 95% CI: 0.026-0.730; p = 0.020). No statistical difference in composite major adverse cardiovascular events (5 vs 14%; p = 0.173) or bleeding (8 vs 6%; Not significant) was observed between PGx-optimal and PGx-suboptimal therapy.