Pharmacogenomics最新文献

Background: Hypertension is a prevalent health concern in Indonesia, with a high percentage of patients unresponsive to ACE inhibitor treatment. Methods: This multicenter case-control study investigated the correlation between ACE I/D and captopril effectiveness in Indonesian hypertensive patients. Hypertensive patients were divided into control (n = 69) and case (n = 73) groups. ACE I/D was identified using PCR and electrophoresis.Results: No significant differences in genotype frequencies or allele distribution were observed. The difference of blood pressure reduction among the three genotypes also lacked statistical significance.Conclusion:  ACE I/D is not significantly associated with blood pressure reduction following captopril therapy in Indonesian hypertensive patients. These results underscore the limited predictive utility of ACE I/D in managing hypertension with captopril.

Introduction: IL-6 and IL-10 may affect the activity of cytochrome P450 (CYP) 3A enzymes involved in tacrolimus (Tac) metabolism. Moreover, the effect of IL-6 and IL-10 on Tac pharmacokinetics may differ with respect to the genetic variations in their genes.Aim: To examine the influence of IL-6 and IL-10 gene polymorphisms on Tac dose requirements and exposure over a 5-year period following kidney transplantation. Univariate and standard multivariate linear regression and Monte Carlo analysis were performed to investigate potential covariates influencing Tac dose-adjusted trough concentration (C₀/D) in various post-transplantation periods.Materials & methods: IL-6 (-174G > C), IL-10 (-1082G > A, -819C > T and -592C > A) genotype, Tac daily dose, C₀, C₀/D and intrapatient variability data were collected from 113 patients.Results: Multivariate regression analysis and accompanied Monte Carlo simulation underscore the importance of considering IL-6 -174G > C and IL-10 -1082G > A gene polymorphisms, alongside Tac metabolic phenotype and post-transplantation period, when tailoring Tac dosage regimen.Conclusion: This study provides valuable insights regarding the individualized adjustment of Tac treatment in various post-transplantation periods.

The study analyzes the risk factors associated with antituberculosis drug-induced liver injury (ATB-DILI), and the relationship between ATB-DILI and NAT2 gene polymorphisms. Out of the 324 included patients, 57 (17.59%) developed ATB-DILI. Age, history of liver disease, alcohol consumption and timing of antituberculosis (ATB) treatment were independent risk factors for ATB-DILI in the patients with tuberculosis (TB; p < 0.05). There was a significant difference in the distribution of NAT2 metabolic phenotypes between the study group and the control group (p < 0.05). The ATB drug treatment for pulmonary TB can cause a high incidence of ATB-DILI. Age, history of liver disease, alcohol consumption and timing of ATB treatment are independent risk factors for ATB-DILI in patients with TB.

HLA alleles, part of the major histocompatibility complex, are strongly associated with adverse drug reactions (ADRs). This review focuses on HLA-B*15:02 and explores its association with ADRs in various ethnic populations and with different drugs, aiming to provide insights into the safe clinical use of drugs and minimize the occurrence of ADRs. Furthermore, the review explores the potential mechanisms by which HLA-B*15:02 may be associated with ADRs, aiming to gain new insights into drug modification and identification of haptens. In addition, it analyzes the frequency of the HLA-B*15:02, genotyping methods, cost-effectiveness and treatment measures for adverse reactions, thereby providing a theoretical basis for formulating clinical treatment plans.

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.

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.