Pharmacogenomics最新文献

Aim: Assess the acceptance of genotype-based pharmacist recommendations made within a pharmacogenetics (PGx) clinic.

Methods: Patients seen by the UF Health PGx clinic between 2017 and 2022 were included in a retrospective chart review. We evaluated CYP2D6/CYP2C19 and three drug classes (opioids, selective serotonin reuptake inhibitors [SSRIs], proton pump inhibitors [PPIs]). Gene-drug pairings were classified as concordant/discordant based on pharmacist recommendations, derived from guidelines. The concordance was compared between baseline, or time that PGx results were available, at 3- and 12-months after the visit. Acceptance of recommendations was inferred by a reduction in discordant gene-drug pairs.

Results: 201 patients with PGx results were seen at the clinic. There were 101 relevant prescriptions at baseline; of these 50 (50%) were discordant based on CYP2C19/CYP2D6 phenotypes. This decreased to 22 (22%); acceptance rate = 56% at 3-months (28 of 50 recommendations accepted), p-value < 0.05. At baseline, there were 28 SSRIs prescriptions, 18 (64%) were discordant versus 7 (25%) at 3-months; acceptance rate = 61%, p-value < 0.05. Of the 60 PPIs prescriptions at baseline, 25 (42%) were discordant, decreasing to 6 (10%) at 3-months; acceptance rate = 76%, p-value < 0.05.

Conclusion: We observed a reduction in discordant gene-drug pairs as a result of PGx pharmacist recommendations acceptance.

Introduction: Polymorphisms in transporter (P-gp, OATP) genes affect digoxin pharmacokinetics and are crucial for predicting toxicity due to its narrow therapeutic index. However, evidence regarding their effects on digoxin serum concentrations remain inconsistent. This systematic review and meta-analysis aimed to evaluate the influence of transporter polymorphisms on digoxin serum concentrations.

Methods: A systematic search of EBSCOhost, Scopus, PubMed, Web of Science and ClinPGx was conducted up to May 2025. Study quality was evaluated using the Newcastle-Ottawa Scale. Mean differences with 95% confidence intervals were calculated for digoxin serum concentrations (C_max, AUC, and SDC) using a random-effects model. Statistical heterogeneity was assessed using the I² statistic, and subgroup analyses were performed.

Results: Nineteen eligible studies were identified. A significant association was observed between ABCB1 C3435T polymorphism and elevated digoxin C_max across multiple genetic models, with the largest effect observed between codominant T/T versus C/C (MD: 0.40 ng/mL; 95% CI: 0.14-0.66). Conversely, opposite associations were observed in the Japanese population, where C allele carriers had higher digoxin AUC_0-4 hr.

Conclusion: The ABCB1 C3435T polymorphism influences digoxin serum concentrations and may inform genotype-guided therapy. However, the limited number of studies in meta-analysis warrants further well-designed studies.This systematic review and meta-analysis was not registered in any protocol registry.

Background: Fluoropyrimidines are among the most useful drugs in oncology with an established record of efficacy and safety. A minority of oncology patients bear genetic variants with reduced activity of the main enzyme catabolizing these drugs, dihydropyrimidine dehydrogenase (DPYD) and may be prone to severe or even lethal adverse effects.

Patients and methods: We reviewed the records of gastrointestinal and breast cancer patients treated in our cancer center for the identification of cases that had DPYD genetic testing for variants and received treatment with fluoropyrimidines. The records of patients fulfilling these criteria were retrieved, and the prevalence of the different variants and their clinical implications and outcomes were recorded.

Results: The overall prevalence of four common DPYD variants was 7.3% (10 of 137 patients). Most prevalent variant was the haplotype HapB3 (five patients, 3.6%), followed by the DPYD p.D949V variant (3 patients, 2.2%), while one patient each (0.7%) had the two null variants DPYD*2A and DPYD*13.

Conclusion: A sizable minority of oncology patients bear variants of DPYD with reduced activity and may be at increased risk of fluoropyrimidine toxicities if treated at full doses. However, variability within the same genotype exists.

Aims: Major depressive disorder (MDD) is highly prevalent among Veterans, who often experience inadequate response to first-line antidepressants. Pharmacogenetic testing may improve treatment selection by identifying genetic variants that affect drug metabolism. This study evaluated the prevalence of pharmacogenetically actionable variants and drug-gene interactions (DGIs) in Veterans with MDD.

Participants and methods: This retrospective chart review included Veterans aged 19-89 years diagnosed with MDD who were prescribed, previously prescribed, or under clinical consideration for future treatment with at least one mental health medication for which actionable pharmacogenetic guidance exists. Medication histories were assessed for DGIs. The primary outcome was the number of medications with at least one actionable DGI.

Results: Among 32 participants (75% male; 59% Black/African American), 88 current or historical pharmacogenetically actionable mental health medications were identified (median 2 per participant; range 0-9). Thirty-eight (43.2%) medications had ≥1 DGI. Eighteen participants (56.3%) carried ≥1 actionable DGI, with a median of 1 (range: 0-8).

Conclusions: Clinically actionable pharmacogenetic variation was highly prevalent in this Veteran cohort. These findings support the integration of preemptive pharmacogenetic testing into psychiatric care; however, further research is needed to evaluate its impact on treatment response, remission rates, and clinical decision-making.

Aim: This systematic review and meta-analysis aimed to investigate the association between ABCG2 polymorphisms and allopurinol response in gout patients.

Methods: A comprehensive search of Scopus, PubMed, Web of Science, EBSCOhost, and the Clinical Pharmacogenomic Resource was conducted for observational studies up to May 2025. Two authors independently screened studies, extracted data, and assessed study quality using the Newcastle-Ottawa Scale. Pooled odds ratios with 95% confidence intervals were calculated using a random-effects model across codominant, dominant, and recessive genetic models. Statistical heterogeneity was evaluated using the I² statistic, and sensitivity analyses were performed.

Results: Six studies met the inclusion criteria for the review, and five were included in the meta-analysis. A significant association was observed between rs2231142 with poor allopurinol response, but not rs10011796. Sensitivity analyses confirmed the robustness of the findings for rs2231142.

Conclusion: The findings suggest that ABCG2 rs2231142 influences allopurinol response. These results underscore the potential of rs2231142 as a predictive genetic marker for allopurinol efficacy and may inform the development of pharmacogenomic guidelines for gout management.This systematic review and meta-analysis was not registered in any protocol registry.

Provider attitudes on the clinical applicability of pharmacogenomics (PGx) are variable. We investigated psychiatry provider perspectives on PGx testing to gauge familiarity, implementation barriers/facilitators, and educational gaps within the Johns Hopkins Health System (JHHS). A 63-question survey was disseminated to psychiatry attending physicians and trainees practicing at JHHS. The survey queried familiarity with PGx testing, its clinical utility, barriers, benefits, the future landscape of PGx, and improvements in PGx implementation. Responses were categorized using a Likert scale and analyzed with Mann-Whitney non-parametric statistical testing. Within our health system, a minority of respondents were aware of PGx resources and there was mixed comfortability in the utilization and interpretation of PGx results. There were mixed opinions regarding the current clinical benefits of PGx testing but there was a desire for further education/training and strong agreement regarding the increased role of PGx in the future of psychiatric practice. Areas where PGx could be improved for greater clinical integration were also identified. While current PGx perspectives are mixed, there is agreement that PGx will play a greater role in psychiatry, highlighting the importance of PGx education and testing integration within a framework which promotes multi-disciplinary consultation to overcome implementation and interpretation challenges.