Pharmacogenetics and genomics最新文献

{"title":"The HTR2A rs6311 and rs6313 polymorphisms and atypical antipsychotics response in schizophrenia: a scoping review.","authors":"Nurul Hidayah, Muthi Ikawati, Mustafa Mahmud Amin, Zullies Ikawati","doi":"10.1097/FPC.0000000000000600","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000600","url":null,"abstract":"<p><p>The HTR2A polymorphisms rs6311 (A-1438G) and rs6313 (T102C) have been thoroughly studied for their impact on atypical antipsychotics (AAPs) responsiveness in schizophrenia. However, the results remain inconsistent owing to the complex genetic and pharmacodynamic interactions. The Joanna Briggs Institute and Preferred Reporting Items for Systematic reviews and Meta-Analyses Extension for Scoping Reviews criteria were followed in this scoping review to map the available data on the association between HTR2A polymorphisms and outcomes. We identified 28 studies published before May 2025. Several studies reported that the rs6311 A allele was more frequently associated with improved treatment response, whereas the G allele was linked to poorer or absent response. In contrast, rs6313 exhibited heterogeneous patterns, with some studies reporting poorer response associated with the C allele and others reporting improved response associated with the T allele. This variability across studies likely reflects differences related to specific AAPs, as well as variations in study design and outcome definitions, rather than population or ethnicity-specific biological effects. Overall, HTR2A variants may contribute to interindividual variability in response to AAPs in schizophrenia. However, the current evidence remains insufficient for clinical application and requires further validation in well-designed and adequately powered studies.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"36 5","pages":"185-194"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631158","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin D receptor regulate placental ABCB1 expression transcriptionally by recruiting coactivator SRC-1.","authors":"Shuran Shao, Yu Yan, Lixia Yang, Gang Li, Fan Ma, Hongyu Duan, Bowen Li, Kaiyu Zhou, Yimin Hua, Yafei Guo, Chuan Wang","doi":"10.1097/FPC.0000000000000605","DOIUrl":"10.1097/FPC.0000000000000605","url":null,"abstract":"<p><strong>Background: </strong>P-glycoprotein (P-gp), the most extensively studied ATP-binding cassette (ABC) transporter, is expressed in the apical membrane of syncytiotrophoblast cells and plays a crucial role in placental drug transport. However, the roles of the vitamin D receptor (VDR) and steroid receptor coactivators (SRCs) family members in VDR-mediated transcriptional regulation of the ABCB1 gene in response to 1,25-dihydroxyvitamin D3 in the placenta remain unclear.</p><p><strong>Methods: </strong>VDR-mediated drug efflux was first examined using VDR-deficient mice. Subsequently, the roles of VDR and SRCs in regulating placental P-gp were investigated via specific deletion of VDR and SRCs in mouse trophoblast cells in vivo, and further validated using transfection assays in placental trophoblast cells in vitro. Additionally, the mechanisms underlying VDR-regulated ABCB1 expression were explored.</p><p><strong>Results: </strong>In this study, we first knocked out the Vdr gene in C57BL/6J mice and observed a significant downregulation of P-gp in the placenta. Furthermore, both gain-of-function and loss-of-function assays demonstrated that VDR promotes P-gp expression in human trophoblast cells. Mechanistically, VDR induces ABCB1 gene transcription by binding to the region 2026-2031 bp upstream of the transcriptional start site in the ABCB1 gene promoter in human trophoblast cells. Moreover, we found that SRCs interact with VDR in trophoblast cell lines, and both in vivo and in vitro studies showed that SRC-1 enhances placental ABCB1 expression. Further investigations confirmed that SRC-1 is an essential transcriptional coactivator for VDR-mediated ABCB1 transactivation in human trophoblast cells.</p><p><strong>Conclusions: </strong>Our findings reveal a novel mechanism regulating placental P-gp expression, which may assist clinicians in ensuring the safety of drug therapy during pregnancy.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"195-208"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variation in SLCO1B1 is associated with methotrexate intolerance symptoms in juvenile idiopathic arthritis patients.","authors":"Felicia Gooden, Lisa J Martin, Marc Sudman, Mara L Becker, Susan D Thompson, Marianna Lucafo, Sofia Sindici Forgiarini, Gabriele Stocco, Serena Pastore, Andrea Taddio, Zachary L Taylor, Laura B Ramsey","doi":"10.1097/FPC.0000000000000622","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000622","url":null,"abstract":"<p><p>Methotrexate (MTX) treatment of juvenile idiopathic arthritis (JIA) is complicated by severe intolerance in approximately 30% of patients. MTX intolerance typically presents as nausea (anticipatory and postdose), vomiting, and behavioral symptoms. Although genetic variants in SLCO1B1 have been associated with MTX toxicity in retrospective studies of inflammatory bowel disease, prospective evaluation of this relationship in JIA patients is lacking. This study examined SLCO1B1-MTX intolerance associations accounting for clinical covariates in a prospective observational cohort of patients receiving standard weekly MTX doses (5-25 mg/m2). We performed a zero-inflated Poisson analysis using forward stepwise inclusion of clinical covariates followed by SLCO1B1 alleles. Among 217 JIA patients who completed the MTX Intolerance Severity Score (MISS) survey at 6 ± 2 months post-MTX initiation, the cohort was predominantly female (69.1%), White (76.5%), and received supplementation with folic acid (70.5%). Over 30% of patients met the threshold for MTX intolerance (MISS ≥ 6), and 62.7% of patients reported any MTX intolerance symptoms (MISS > 0). The SLCO1B1*37 allele was associated with lower odds of MISS > 0 (odds ratio = 0.60, P = 0.046) and a lower reported MISS score (incidence rate ratio = 0.74, P < 0.001) among individuals with non-zero intolerance, suggesting protection from MTX intolerance symptoms. These associations were consistent in sensitivity analyses stratified by folic acid supplementation. Further validation of these findings is needed to support future pharmacogenetic-guided MTX dosing strategies, including evaluation of other SLCO1B1 alleles.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DPYD polymorphisms in Native populations from the Brazilian Amazon: the absence of the variants in currently recommended clinical genotyping panels.","authors":"Guilherme Suarez-Kurtz, Paulo C Basta, Jamila Alessandra Perini","doi":"10.1097/FPC.0000000000000611","DOIUrl":"10.1097/FPC.0000000000000611","url":null,"abstract":"<p><strong>Objectives: </strong>We examined the distribution of clinically-relevant DPYD polymorphisms in Yanomami and Munduruku individuals, from Indigenous reservation areas in the Brazilian Amazon. The estimated proportion of Native ancestry exceeded 90% in all participants.</p><p><strong>Methods: </strong>Eight DPYD single nucleotide variants (SNVs), including rs3918290, rs55886062, rs67376798, and rs75017182, widely recognized for their established associations with fluoropyrimidine-induced toxicity, plus rs115232898, rs2297595, rs1801265, and rs4294451 were genotyped, using Taqman probes. The distribution of haplotypes comprising rs1801265, rs2297595, and rs75017182 was assessed.</p><p><strong>Results: </strong>Six variants, namely rs3918290, rs55886062, rs67376798, rs75017182, rs115232898, and rs2297595, were absent in the Yanomami and Munduruku cohorts. In striking contrast, rs1801265 and rs4294451 were common, with minor allele frequency (MAF) ranging between 0.41 (Yanomami) and 0.47 (Munduruku); these SNVs were in perfect (Yanomami) or strong (Munduruku) linkage disequilibrium. Regarding haplotypes comprising rs1801265, rs2297595, and rs75017182, only two were observed: one with the three reference alleles (T-A-C) and the other (C-A-C) with the variant rs1801265 C allele (frequency 41% in Yanomami and 47% in Munduruku).</p><p><strong>Conclusion: </strong>The variants prioritized in the Clinical Pharmacogenetics Implementation Consortium and Dutch Pharmacogenetics Working Group guidelines, namely rs3918290, rs55886062, rs67376798, and rs75017182 were not detected in the Munduruku and Yanomami cohorts. Thus, pharmacogenetic screening of such variants would not provide reliable pharmacogenetic-guided recommendations for fluoropyrimidine dosing in the enrolled Native groups, and possibly other Amerindian ethnicities and admixed Latin American populations with major Native ancestry. DPYD SNVs rs1801265 and rs4294451 were quite common (MAF = 0.41-0.47) and in perfect or nearly complete linkage disequilibrium, which might result in reduced risk of fluoropyrimidine-induced toxicity.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"236-240"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148302577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating the impact of SDHAF3 p.F53L genetic variant on clinically significant QTc prolongation in patients prescribed high-risk medications: a retrospective pharmacogenetic study.","authors":"Ahmed Aalibraheem, Ana I Lopez-Medina, Choudhary Anwar A Chahal, Jasmine A Luzum","doi":"10.1097/FPC.0000000000000610","DOIUrl":"10.1097/FPC.0000000000000610","url":null,"abstract":"<p><p>Drug-induced QT prolongation (diQTP) can lead to rare, but potentially fatal adverse effects of many medications, yet individual susceptibility varies due to both clinical and genetic factors. SDHAF3 p.F53L (rs62624461) is a genetic variant that plays a role in mitochondrial function and was previously associated with diQTP in one small prior study. Therefore, the objective of this retrospective pharmacogenetic study was to evaluate whether SDHAF3 p.F53L is associated with clinically significant diQTP. Data were obtained from the Michigan Genomics Initiative, which links genotype information with electronic health records at Michigan Medicine. Adult patients with available genotype and electrocardiogram data who received at least one high-risk QT-prolonging drug between 2001 and 2022 were included. The analysis was limited to 5848 patients of European ancestry, of whom 320 (5.5%) were carriers of the SDHAF3 p.F53L variant. QT prolongation was defined as a QTc greater than or equal to 500 ms or an increase greater than 60 ms from baseline during high-risk QT-prolonging drug prescription. Logistic regression under a dominant genetic model assessed associations between variant carrier status and diQTP, with and without propensity score adjustment. Baseline demographics and comorbidities were similar between carriers and noncarriers. No significant association was observed between SDHAF3 p.F53L and diQTP [unadjusted odds ratio (OR) = 1.06, 95% confidence interval (CI) = 0.76-1.48, P  = 0.742; adjusted OR = 1.05, 95% CI = 0.74-1.51, P  = 0.773]. These results suggest that SDHAF3 p.F53L does not meaningfully influence diQTP risk in a large, real-world clinical cohort. Future studies should examine this variant across diverse populations.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"241-244"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148259086","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Low expression of ZFP36L2 causes glucocorticoid resistance in childhood T-cell acute lymphoblastic leukemia.","authors":"Yuening Xiang, Mengyan Wang, Shao Xie, Jing Wu, Lin Li, Rongsheng Zhang, Wenxin Ou, Shuiyan Wu, Xinni Bian, Xiaowen Qian, Hongsheng Wang, Feng Zhang, Shaoyan Hu, Allen Eng-Juh Yeoh, Hui Zhang, Xiaowen Zhai, Maoxiang Qian","doi":"10.1097/FPC.0000000000000607","DOIUrl":"10.1097/FPC.0000000000000607","url":null,"abstract":"<p><strong>Objective: </strong>Glucocorticoids (GCs) are essential for the therapy of acute lymphoblastic leukemia (ALL), but glucocorticoid resistance remains a major clinical challenge, and its molecular mechanisms are not fully understood. This study aimed to investigate the role of ZFP36L2, an RNA-binding protein and potential driver gene in T-ALL, in regulating glucocorticoid sensitivity in ALL.</p><p><strong>Methods: </strong>ZFP36L2 expression in ALL were reanalyzed from RNA sequencing data, and the correlation between ZFP36L2 expression and clinical outcomes in ALL patients was analyzed. ZFP36L2 was knocked down in T-ALL cells to observe its effects on glucocorticoid resistance and related signaling pathways. The effect of GCs combined with γ-secretase inhibitor N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT) or MEK inhibitor trametinib on drug sensitivity was detected in vitro .</p><p><strong>Results: </strong>ZFP36L2 expression was significantly lower in T-ALL than in B-ALL, and low ZFP36L2 expression was associated with poor early disease responses and higher relapse risk in ALL. ZFP36L2 knockdown in T-ALL cell lines significantly increased glucocorticoid resistance, weakened glucocorticoid receptor upregulation, impaired apoptosis, reduced Bcl-2 interacting mediator of cell death induction, and repressed BCL2 downregulation. Moreover, ZFP36L2 was critical for glucocorticoid-mediated suppression of the NOTCH1-HES1 and mitogen-activated protein kinase pathway. Notably, combined treatment with GCs and DAPT or trametinib enhanced drug sensitivity in vitro . Mechanistically, ZFP36L2 directly binds to the UAUUUAUU motifs in the 3' untranslated regions of BCL2, Bcl-2 interacting mediator of cell death, and NOTCH1 mRNAs, thereby regulating their stability.</p><p><strong>Conclusion: </strong>These findings demonstrate that ZFP36L2 is a potential regulator of glucocorticoid responsiveness in T-ALL. Combining GCs with DAPT or trametinib offers a potential therapeutic strategy for T-ALL patients, especially those with ZFP36L2 mutations or low ZFP36L2 expression.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"222-235"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The role of pro-inflammatory cytokine gene polymorphisms in major depressive disorder: a systematic review.","authors":"Yuvapriya Kalidasan, Vettriselvi Venkatesan, Suvarna Jyothi Kantipudi, Ilangovan Ramachandran","doi":"10.1097/FPC.0000000000000609","DOIUrl":"10.1097/FPC.0000000000000609","url":null,"abstract":"<p><p>Major depressive disorder (MDD) is a multifactorial psychiatric disorder increasingly associated with immune-inflammatory mechanisms. Pro-inflammatory cytokines, particularly tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), have been implicated in the pathophysiology of MDD through their influence on neuroinflammation, neurotransmitter regulation, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. This systematic review aimed to evaluate the association between TNF-α and IL-1β gene polymorphisms and susceptibility to MDD, treatment response, and related clinical outcomes. A systematic literature search was conducted in PubMed, Embase, and ScienceDirect databases from inception to March 2026, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies investigating TNF-α and IL-1β gene polymorphisms in clinically diagnosed MDD patients were included. Case-control studies published in English involving adult human participants were considered eligible. Data regarding study design, population, polymorphisms, and clinical outcomes were extracted and qualitatively synthesized. A total of 172 records were identified, of which nine studies met the inclusion criteria. Included studies primarily investigated TNF-α rs1800629 and IL-1β rs16944 polymorphisms across diverse populations. Several studies reported significant associations between these polymorphisms and increased susceptibility to MDD, suicide risk, severity of depressive symptoms, age of onset, and antidepressant treatment response. However, some studies reported no statistically significant associations, indicating heterogeneity across ethnic groups and study populations. Variability in age, medication status, and environmental stressors may have contributed to inconsistent findings. The findings of this systematic review support the involvement of inflammatory cytokine gene polymorphisms in the pathophysiology of MDD, particularly TNF-α and IL-1β variants. These polymorphisms may contribute to depression susceptibility and treatment response through immune-inflammatory mechanisms. Further large-scale, ethnically diverse studies incorporating gene-environment interactions and next-generation sequencing approaches are needed to validate cytokine-related genetic biomarkers in MDD.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"177-184"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148265454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence of CYP2C19 phenotypes in patients undergoing a hiatal hernia repair.","authors":"Abdel-Rahman Naser, Keouna Pather, Erin M Mobley, Brandon Climenhage, Emily J Cicali, Larisa H Cavallari, Jana M Sacco, Ruchir Puri","doi":"10.1097/FPC.0000000000000599","DOIUrl":"10.1097/FPC.0000000000000599","url":null,"abstract":"<p><strong>Objectives: </strong>Gastroesophageal reflux disease is primarily treated with proton pump inhibitors (PPIs), which are metabolized by cytochrome P450 2C19 ( CYP2C19 ) in the liver. CYP2C19 polymorphisms affect PPI plasma levels, with rapid (2-27%) and ultra-rapid (<1-5%) metabolizers needing higher doses, while poor (3-15%) and intermediate (27-47%) metabolizers require lower doses for therapeutic effectiveness. Antireflux surgery is recommended for patients refractory to medical therapy or with symptomatic hiatal hernias.</p><p><strong>Methods: </strong>This is a multisite retrospective review of adult patients from 2012 to 2023 diagnosed with gastroesophageal reflux disease who underwent hiatal hernia operations and completed CYP2C19 testing. CYP2C19 phenotypes were grouped as poor metabolizer/intermediate metabolizer, normal metabolizers, or rapid metabolizer/ultra-rapid metabolizer. Hiatal hernia size was classified as small, medium, or large based on preoperative and intra-operative findings. Descriptive statistics were used.</p><p><strong>Results: </strong>Eighty patients [female: 66%, median age: 60.5 (interquartile range 53.3-67.0) years, 90% White, 6% Hispanic] had CYP2C19 testing and underwent a hiatal hernia repair. CYP2C19 phenotypes were poor metabolizer (4%), intermediate metabolizer (24%), normal metabolizers (30%), rapid metabolizer (31%), and ultra-rapid metabolizer (11%). About 28% were grouped as poor metabolizer/intermediate metabolizer and 43% as rapid metabolizer/ultra-rapid metabolizer. Among patients with small ( n  = 41) and medium ( n  = 23) hernias, 39% and 57%, respectively, were classified as rapid metabolizer/ultra-rapid metabolizer, suggesting they were resistant to PPIs.</p><p><strong>Conclusion: </strong>The prevalence of rapid metabolizer/ultra-rapid metabolizer CYP2C19 phenotypes in patients undergoing antireflux surgery is higher than generally reported in the general population. These patients could potentially benefit from higher PPI doses or surgical intervention if ineffective. Prospective multisite studies with diverse, representative samples are needed to confirm these findings.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"209-214"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148138671","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knowledge and perspectives on pharmacogenomic-guided antidepressant treatment among psychiatrists and primary care practitioners.","authors":"Kendall T Schmidt, Hetanshi Naik, Thuy-Mi P Nguyen, Jeffrey R Bishop, Chad A Bousman, Ajeet B Singh, Teri E Klein, Stuart A Scott","doi":"10.1097/FPC.0000000000000608","DOIUrl":"10.1097/FPC.0000000000000608","url":null,"abstract":"<p><strong>Objectives: </strong>This study compared psychiatrist and primary care practitioner (PCP) perspectives on pharmacogenomics and barriers to its use in guiding antidepressant prescribing.</p><p><strong>Methods: </strong>Psychiatrists and PCPs across the USA were invited to complete an anonymous 31-item online survey that collected demographic information, knowledge and experience with pharmacogenomics, and attitudes and perspectives on the clinical use of pharmacogenomics.</p><p><strong>Results: </strong>Psychiatrists ( n  = 36) reported greater familiarity and experience with antidepressant pharmacogenomics than PCPs ( n  = 11); however, both lacked familiarity with implementing pharmacogenomic testing and related clinical resources. Identified barriers to testing among psychiatrists focused predominantly on concerns over clinical utility and applicability to patients. The reported barriers among PCPs were lack of test information and lack of knowledge on how to order and how to utilize pharmacogenomic results. However, all respondents supported multigene panel-based pharmacogenomic testing and including all potentially impacted medications in test reports.</p><p><strong>Conclusion: </strong>Despite a low overall response rate and disproportionate survey participation between provider types, this study identified knowledge and experience as current barriers for psychiatrists and PCPs to implement pharmacogenomic-guided antidepressant prescribing. Importantly, both clinician groups indicated interest in pharmacogenomics education, professional support for implementation, and panel-based pharmacogenomic testing with comprehensive medication management reporting.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"215-221"},"PeriodicalIF":1.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252630","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical outcomes stratified by CYP2C19 phenotypes in intracranial artery stenting patients with genotype-guided antiplatelet regimens: a real-world single-center retrospective cohort study.","authors":"Yunzhen Hu, Meihua Lin, Qinqin Zhao, Ziqi Xu, Liang Shen, Huaiwu Yuan","doi":"10.1097/FPC.0000000000000618","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000618","url":null,"abstract":"<p><strong>Objectives: </strong>Clinical trial evidence is scarce for optimal antiplatelet strategies in patients undergoing intracranial artery stenting with CYP2C19 loss‑of‑function alleles, especially regarding the efficacy‑safety balance.</p><p><strong>Methods: </strong>This single‑center retrospective study enrolled patients receiving genotype‑guided antiplatelet regimens for intracranial stenting between January and December 2023, with 6‑month follow‑up. Clinical outcomes were compared across CYP2C19 phenotypes.</p><p><strong>Results: </strong>Among 205 patients, 46.8% were normal metabolizers, 40.5% intermediate metabolizers, and 12.7% poor metabolizers. Aspirin-clopidogrel was prescribed for all normal metabolizers, 80.7% intermediate metabolizers, and 19.2% poor metabolizers. No intergroup differences were observed in risks of ischemic stroke/transient ischemic attack (TIA), cardiovascular events, intracerebral hemorrhage (ICH), or any bleeding (all P > 0.05). In intermediate metabolizers and poor metabolizer subgroups, ischemic stroke/TIA rates were 11.1% in the aspirin-clopidogrel group and 9.68% in the aspirin-ticagrelor group, with no significant difference compared to normal metabolizers (4.17%). ICH rates were 1.39% in the aspirin-clopidogrel group and 6.45% in the aspirin-ticagrelor group, showing no significant difference versus normal metabolizers (1.04%). Multivariate logistic analysis found the number of stents (odds ratio [OR] = 2.70; 95% confidence interval [CI] = 0.89-6.95; P = 0.043) was a risk factor for ischemic stroke/TIA. Ticagrelor-based dual antiplatelet therapy (DAPT; OR = 10.57; 95% CI = 1.00-111.7; P = 0.05) and baseline l ow-density lipoprotein cholesterol (LDL-C; OR = 7.22; 95% CI = 1.80-29.01; P = 0.005) were associated with ICH risk.</p><p><strong>Conclusion: </strong>Antiplatelet regimens were adjusted for a subset of intermediate metabolizers and poor metabolizers prior to stenting, and the 6-month clinical outcomes were comparable across normal metabolizers, intermediate metabolizers, and poor metabolizers. The stent number was associated with ischemic stroke/TIA risk; baseline LDL-C and ticagrelor-based DAPT with ICH risk. These exploratory findings need validation in adequately powered studies.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}