Pharmacogenomics最新文献

Aim: This study aims to better understand the utility of pharmacogenomic (PGx) testing for the rare disease, Prader-Willi syndrome (PWS).

Methods: Individuals with PWS received PGx testing, and their caregivers were surveyed 1 month after receiving results (n = 42) and 6-months after receiving results (n = 38). A subset of respondents (n = 9) also participated in qualitative interviews.

Results: After receiving the PGx results, only one caregiver participant (2.27%) reported making medication changes. Eighty percent of caregiver participants stated the most valuable aspect of the PGx results was the information it provided about future medications their child may need. Interview participants discussed how the report gave them reassurance or verification of their current medication regimen. Only 36.59% of caregiver participants shared PGx results with their child's healthcare providers during the six-month follow-up period. Interview participants described reasons for not sharing the PGx report, including that nothing in the report prompted them to do so, or that they believed providers would not use it.

Conclusion: PGx results are perceived as valuable to the PWS population, but sharing PGx results with healthcare providers was limited at the six-month time point.

Aim: To determine Penn Medicine patients' and gynecologic providers' knowledge and attitudes about pharmacogenetic (PGx) testing.

Methods: In this cross-sectional study, surveys were distributed to patients and gynecologic surgeons who participated in a randomized, prospective, open-label pilot study using PGx results to assist in the selection of postoperative analgesic medications. The primary objective was to understand patient- and provider-level factors that impact PGx test adoption.

Results: A majority (67%) of patients planned to share their results with their healthcare providers, and many patients (52%) were interested in having a PGx specialist further explain their results. Few (12%) gynecologic surgeons were confident in their ability to use PGx results to guide medication prescribing. The most common barrier identified was lack of training or experience with PGx testing (91%).

Conclusion: Patients want to share their results with their providers and desire further explanation. However, gynecologic surgeons do not feel prepared to utilize these PGx results to make prescribing decisions. Therefore, efforts focused on PGx education for physicians are essential prior to implementing testing into clinical practice.

Aim: Pharmacogenomics enables treatments to be tailored to individual genetic profiles, optimizing efficacy while reducing adverse effects. The Clinical Pharmacogenetics Implementation Consortium (CPIC) classifies gene-drug pairs by their level of evidence. Level A and B pairs are considered actionable, indicating that prescribers should (A) or could (B) modify therapy.

Materials and methods: This cross-sectional study aimed to assess the prevalence of actionable CPIC variants in the Montreal Heart Institute (MHI) Hospital Cohort. Genotyping was performed at the MHI Beaulieu-Saucier Pharmacogenomics Center using Agena's MassARRAY and Illumina's Global Screening Array. Genes ABCG2, CYP2B6, CYP2C9, CYP2C19, CYP2D6, CYP3A5, CYP4F2, DPYD, HLA-A, HLA-B, SLCO1B1, TPMT, UGT1A1, and VKORC1 were analyzed in 10,082 participants.

Results: Participants had an average of 3.9 genes with actionable variants, and among the full cohort, 99.7% carried at least one actionable variant. Of the 65 CPIC level A or B gene-drug pairs evaluated, 57 involved medications used by at least one participant. Nearly 40% of participants had at least one actionable gene-drug pair - that is, they were taking a medication for which they carried an actionable variant.

Conclusion: This study confirms the high prevalence of actionable genetic variants in individuals with or at high risk of cardiovascular diseases.

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.

Aims: Sequential Anthracycline-Taxane chemotherapy is standard treatment for BC. This study examines the combined impact of low BMI and CYP polymorphisms on treatment response.

Method: BMI was assessed before chemotherapy, and clinical response was evaluated using RECIST v.1. Four SNPs in CYP2C9, CYP2C19, and CYP3A4 gene were analyzed in 148 samples using PCR-RFLP.

Results: CYP2C19 (G681A) was significantly associated with treatment non-responsiveness in all genetic models namely dominant (OR11.119; 95%CI [5.103-24.228], p < 0.0001), recessive (15.818; [4.548-55.015]; p < 0.0001), codominant (χ² 48.229; p < 0.0001). No significant association was found in other two genes CYP2C9 (C430T, A32621C) and CYP3A4 (A392G). When combined with BMI, the CYP2C19 AA genotype showed significant associations with poor treatment response for low BMI group across all genetic models: dominant (9.60; [2.892-31.864]; p < 0.0001), recessive (1.473; [1.404-2.164]; p < 0.001), and codominant (χ² 18.897; p < 0.0001) and AA associated with lowest PFS: 38 months; HR >1. OS (39.79 months; p = 0.039) were lowered among GA genotype with increased HR (HR 3.78; p = 0.031).

Conclusion: AA genotype at G681A in low BMI patients showed the poorest chemotherapy response and lowest PFS (HR>1). CYP2C19 variants (AA) may serve as predictive markers for non-responsiveness towards AC-T chemotherapy in low BMI BC patients, highlighting the need for genetic counselling and nutritional support to improve treatment outcomes.

Introduction: Precision medicine is the future of healthcare, and pharmacists are well-positioned to play a key role in pharmacogenomics (PGx). Experiential learning offers valuable opportunities to gain hands-on experience in clinical PGx practices. This study aimed to explore experiential learning opportunities in PGx for pharmacy education.

Methods: Four PGx clinics in the United States of America, which provide PGx services, were observed to assess the potential for experiential learning. Qualitative data were collected through observations of PGx clinic consultations and semi-structured interviews with four pharmacists, one at each site. This approach provided insight into the practice-based learning opportunities in PGx clinics to explore experiential learning.

Results: Multiple experiential learning opportunities were identified, including activities to develop knowledge and skills; conduct research; collaborate with an interprofessional team; create patient education resources; provide patient and healthcare education; provide comprehensive care; develop evidence-based medicine skills, including the use of PGx resources; address ethical, legal, and social implications of PGx, and leadership.

Conclusion: Pharmacogenomics clinics offer valuable experiential learning opportunities for pharmacy education. Collaboration between healthcare and higher education institutions is essential to create these opportunities, ensuring the development of pharmacists who are prepared to meet future healthcare needs.

Introduction: Transient ischemic attack (TIA) or ischemic stroke (IS) patients may have recurrent stroke incidents, especially when carrying CYP2C19 Loss-of-Function (LoF) alleles and taking clopidogrel. Recent studies suggest using alternative antiplatelets, e.g., prasugrel, ticagrelor, in these patients. However, the aggregated risk of recurrent stroke or composite vascular events in CYP2C19 genotype-guided prasugrel/ticagrelor against clopidogrel therapy in such TIA/IS patients remained unexplored.

Methods: A database search was performed to retrieve relevant studies. RevMan software was used to calculate the risk ratio (RR), considering p < 0.05 statistically significant.

Result: Six studies (14,124 TIA/IS patients) were considered. TIA/IS patients carrying CYP2C19 LoF alleles on ticagrelor/prasugrel therapy were associated with a significant reduction in the risk of composite vascular events (RR 0.76, 95% CI 0.66-0.89; p = 0.0004) and recurrent stroke (RR 0.76, 95% CI 0.64-0.90; p = 0.002) compared to the clopidogrel therapy. However, the bleeding events did not differ significantly (RR 0.91, 95% CI 0.65-1.27; p = 0.58) between the treatment groups.

Conclusion: TIA/IS patients inheriting CYP2C19 LoF alleles taking ticagrelor/prasugrel may significantly optimize the overall clinical benefits compared to those who are taking clopidogrel by reducing composite vascular events and recurrent stroke without elevating the risk of bleeding events.

Aims: To screen and validate rare variants in the protoporphyrin IX (PPIX)-metabolizing pathway associated with anti-tuberculosis drug-induced hepatitis (AT-DIH).

Methods: A two-stage matched case-control study was conducted. Firstly, a 1:1 matching design (50 cases and 50 controls) was adopted to screen for rare variants using whole exome sequencing (WES). Secondly, a 1:4 matching design (132 cases and 528 controls) was employed to validate these rare variants via TaqMan genotyping. The association between these variants and AT-DIH risk was evaluated using odds ratios (ORs) with 95% confidence intervals (CIs), with the false discovery rate (FDR) applied for multiple comparison correction.

Results: The optimal sequence kernel association test (SKAT-O) and set-based tests identified 19 and 1 genes significantly associated with AT-DIH, respectively. The nuclear receptor coactivator 3 (NCOA3) gene was detected by both methods (SKAT-O: p = 0.002; set-based tests: p = 0.038), and seven algorithms identified four NCOA3 rare variants as deleterious. Further validation showed that the CC genotype of rs2230782 increased the risk of AT-DIH (OR = 15.074, 95%CI: 1.442-157.525, FDR p = 0.046), and this association remained significant in the two-stage combined analysis (3 cases and 1 control with CC genotype, OR = 14.832, 95%CI: 1.422-154.695, FDR p = 0.048).

Conclusions: NCOA3 rs2230782 is associated with AT-DIH in Chinese anti-tuberculosis patients.