Pharmacogenetics and genomics最新文献

{"title":"Impact of CYP3A5 genotype on tacrolimus pharmacokinetics and clinical outcomes in pediatric patients with Henoch-Schönlein purpura nephritis.","authors":"Huiying Li, Na Li, Xiaoling Tang, Fashuang Li, Danyang Ren, Jing Zong, Caixia Tu, Linbo Li, Lilin Zhang, Shaochun Yu","doi":"10.1097/FPC.0000000000000604","DOIUrl":"10.1097/FPC.0000000000000604","url":null,"abstract":"<p><strong>Aim: </strong>This study aimed to evaluate the impact of CYP3A5 gene polymorphism on the pharmacokinetics, therapeutic efficacy, and safety of tacrolimus in pediatric patients with Henoch - Schönlein purpura nephritis (HSPN).</p><p><strong>Methods: </strong>This study used a retrospective observational design to investigate pediatric patients with HSPN treated with tacrolimus. The polymorphism at the CYP3A5 was detected using PCR technology. The concentration of tacrolimus was quantitatively determined by ultra-performance liquid chromatography. The study systematically analyzed the impact of CYP3A5 gene polymorphism on the pharmacokinetic parameters of tacrolimus (including trough concentration C0 , dose D , and dose-corrected concentration C0 / D ), clinical efficacy, and adverse reactions.</p><p><strong>Results: </strong>The study enrolled 103 pediatric patients. Comparative analysis revealed that patients with CYP3A5*1/*1 or *1/*3 genotypes exhibited significantly lower tacrolimus C0 and C0 / D at various time points when compared with CYP3A5*3/*3 g enotype carriers. Furthermore, CYP3A5*1 expressers ( CYP3A5*1/*1 and *1/*3 ) demonstrated markedly reduced tacrolimus C0 and C0 / D levels across multiple time points relative to CYP3A5*3 nonexpressers ( CYP3A5*3/*3 ). However, CYP3A5 genetic polymorphisms did not demonstrate significant associations with clinical efficacy or adverse reactions.</p><p><strong>Conclusion: </strong>The polymorphism of the CYP3A5 gene may provide information on the pharmacokinetics of tacrolimus in pediatric with HSPN, but its clinical relevance has not yet been demonstrated.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"245-257"},"PeriodicalIF":1.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147988647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Individualized perampanel response and efficacy in patients with refractory epilepsy: the need for ATP-binding cassette B1 genotyping and therapeutic drug monitoring to work in tandem.","authors":"Ting Zhao, Hong-Jian Li, Hui-Lan Zhang, Jing Yu, Yan Sun, Lu-Hai Yu, Lu-Feng Cheng","doi":"10.1097/FPC.0000000000000614","DOIUrl":"10.1097/FPC.0000000000000614","url":null,"abstract":"<p><strong>Objective: </strong>This study analyzed the correlation and differences between the gene polymorphisms of ATP-binding cassette B1 ( ABCB1 ), which encode the efflux drug transporter P-glycoprotein, and the efficacy and plasma concentration of perampanel (PER) in patients with refractory epilepsy.</p><p><strong>Methods: </strong>Plasma samples were collected from 115 patients with epilepsy who received PER treatment for at least 21 days. The ABCB1 genotypes were detected using first-generation Sanger sequencing, and the PER plasma concentration was measured using ultra-high performance liquid chromatography-mass spectrometry.</p><p><strong>Results: </strong>The overall efficacy of PER in treating patients with refractory epilepsy was observed in 64.3% of patients. The ABCB1 rs2032582 gene polymorphisms were significantly associated with the therapeutic efficacy of PER in refractory epilepsy. When compared with patients with the wild-type homozygous genotype, the plasma concentrations of PER were significantly higher for patients with the P-glycoprotein-encoding ABCB1 rs2032582 and ABCB1 rs1045642 mutant genotypes ( P  < 0.05). When the plasma concentration of PER exceeded 305 ng/ml, patients more effectively responded to PER treatment (area under the curve: 0.614, P  < 0.05).</p><p><strong>Conclusion: </strong>ABCB1 gene polymorphisms are important predictors of effective with PER treatment and serve as factors that affect the achievement of therapeutic plasma concentrations of PER, and they have contrasting effects.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"276-289"},"PeriodicalIF":1.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148520732","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, perception, and attitude toward clinical implementation of pharmacogenomics among healthcare professionals in Pakistan: a cross-sectional study.","authors":"Bushra Waheed, Asif Jan, Basmah Abdulaziz Albabtain, Rani Akbar, Nafees Ahmad, Tahir Muhammad, Muhammad Usman Ijaz","doi":"10.1097/FPC.0000000000000612","DOIUrl":"10.1097/FPC.0000000000000612","url":null,"abstract":"<p><strong>Background: </strong>As precision medicine advances, integrating pharmacogenomics (PGx) into routine practice requires coordinated efforts among healthcare professionals. This study evaluated the knowledge, attitudes, and perceptions of Pakistani physicians, nurses, and pharmacists toward PGx implementation.</p><p><strong>Methods: </strong>This cross-sectional, prospective, web-based study was carried out employing a self-administered questionnaire involving 1560 respondents across Pakistan.</p><p><strong>Results: </strong>The respondents comprised 70% males. Most respondents (95%) were in the age range of 20-40 years, and the majority held a bachelor's degree (94%). Pharmacists comprised the largest group (64%), followed by physicians (24%) and nurses (12%). Participants responded from academia (33%), healthcare settings (46%), industry (14%), and regulatory authorities (6.5%). Most (89%) lack exposure to PGx, and only 10% had PGx training. Sixty-one percent had under 5 years of experience. Only 12.8% demonstrated good knowledge, yet positive attitudes (66.6%) and perceptions (67%) predominated. Knowledge was not associated with attitude or perception but was significantly linked with training and experience. Training and experience were significantly tied to positive perceptions, with years of experience showing more consistent associations across domains.</p><p><strong>Conclusion: </strong>While Pakistani healthcare professionals hold positive attitudes toward PGx, baseline knowledge remains low. Training and experience are key drivers of readiness. There is an urgent need for structured training, professional workshops, and curriculum integration to support PGx adoption in Pakistan.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"266-275"},"PeriodicalIF":1.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148387900","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 and clinical impact of the uncommon DPYD c.257C>T (Pro86Leu) variant in a multiethnic cohort receiving fluoropyrimidine therapy.","authors":"Marie-Jeanne Carp, Gil Ring, Ithai Waldhorn, Alexandra Shempliner, Talia Schantzer, Noa Mor, Larisa Ryvo, Daniel Kurnik, Edna Efrati","doi":"10.1097/FPC.0000000000000616","DOIUrl":"10.1097/FPC.0000000000000616","url":null,"abstract":"<p><p>Pre-emptive genotyping and genotype-guided dose adjustments are generally recommended for seven hypofunctional polymorphisms in the DPYD gene that are associated with fluoropyrimidine toxicity. However, targeted genotyping may miss uncommon and population-specific hypofunctional variants. Therefore, in 2021, we replaced conventional targeted genotyping with comprehensive DPYD exome sequencing. The objective of the current study was to identify uncommon hypofunctional variants and assess their association with fluoropyrimidine toxicity. In a cohort of 762 consecutive patients pre-emptively genotyped between 2021 and 2025, among the seven established risk variants, we identified *2A and HapB3 at their expected minor allele frequencies (MAF), but no carriers of any of the five other established risk variants. Interestingly, four patients were heterozygous for the rare missense c.257C>T variant (Pro86Leu; rs568132506), previously associated with fluoropyrimidine toxicity. The MAF (2.62 × 10 -3 ) was similar to that previously described in Middle Eastern populations but 26-fold higher than in the gnomAD global population. Three of the carriers (75%) developed grade 3-4 fluoropyrimidine toxicity after one or two cycles, corresponding to a relative risk of 14.5 (95% confidence interval: 5.0-30.4, P  = 0.0009) compared with a control cohort without hypofunctional DPYD variants. Our findings add to the growing body of evidence indicating that DPYD c.257C>T may be associated with severe fluoropyrimidine toxicity. Future studies should examine the clinical utility of including uncommon but potentially actionable variants, such as c.257C>T, into pre-emptive genotyping algorithms. This may be particularly important in multiethnic populations in which these variants can be more prevalent than those variants for which pre-emptive genotyping is generally recommended.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"290-294"},"PeriodicalIF":1.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860637","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 polymorphisms in ABCB1 and CEP72 genes as pharmacogenetic markers in patients receiving vincristine-based chemotherapy: a preliminary Indian context exploratory study.","authors":"Ramya Sugumar, Harpreet Kaur, Latha M S, Jullius X Scott, Manickavasagam M","doi":"10.1097/FPC.0000000000000606","DOIUrl":"10.1097/FPC.0000000000000606","url":null,"abstract":"<p><strong>Introduction: </strong>Vincristine is limited by its adverse effect of peripheral neuropathy with only a few inconclusive reports of its genetic occurrence. Therefore, the present research work was intended to identify the distribution of rs1045642 polymorphism in ABCB1 gene and rs924607 polymorphism in CEP72 gene, and their association with clinically documented neurological adverse drug reactions to vincristine.</p><p><strong>Methods: </strong>Seventy-five children below 18 years diagnosed with acute lymphoblastic leukemia receiving vincristine were followed for 6 months and analyzed for correlation with vincristine-associated neuropathy.</p><p><strong>Results: </strong>Twenty of 75 patients were homozygous for the risk allele (TT at rs924607) of CEP72 genotype and 25 of 75 patients were homozygous for the risk allele (TT at rs1045642) of ABCB1 genotype. Among patients with the high-risk ABCB1 genotype (TT at rs1045642), 13 of 25 (52%) developed at least one episode of grade 1-3 neuropathy, and had a statistically significant 4.3 times risk of developing neurotoxicity in comparison to patients with the ABCB1 CC or CT genotypes [10 of 50 (20%) patients, odds ratio: 4.3, 95% confidence interval: 1.5-12.3; P = 0.0060]. The patients receiving average dose of vincristine of greater than or equal to 2 mg/m 2 (58.3%) when compared to those receiving an average dose of less than 2 mg/m 2 (25.4%) had 4.1 times risk of developing neurotoxicity (odds ratio: 4.1, 95% confidence interval: 1.1-14.8; P = 0.0304).</p><p><strong>Conclusion: </strong>This study emphasizes the significant association of ABCB1 genotype (TT at rs1045642) with vincristine-associated neuropathy and highlights the relevance of higher average doses of vincristine in causing neurotoxicity.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"258-265"},"PeriodicalIF":1.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148252668","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":"Association of UGT and CYP genotype-predicted activity with tyrosine kinase inhibitor toxicity.","authors":"April T Moy, Lia E D'Angelo, Daniel L Hertz","doi":"10.1097/FPC.0000000000000613","DOIUrl":"10.1097/FPC.0000000000000613","url":null,"abstract":"<p><p>Associations between genetically predicted activity of metabolic enzymes and risks of adverse events from tyrosine kinase inhibitors (TKIs) may inform dosing to optimize treatment outcomes in patients with cancer. The goal of this study is to investigate the associations between UGT1A1, CYP3A4, and CYP1A2 activity and toxicity from nilotinib and pazopanib treatment. A retrospective pharmacogenetic association study was conducted in 117 participants of the Michigan Genomics Initiative who received pazopanib ( n  = 103) or nilotinib ( n  = 14). Clinical information, including patients' disease, treatment, and toxicity was collected via retrospective review of medical records. No associations were found between the genetically predicted activity of any of the three enzymes and the composite endpoint of severe toxicity or treatment modifications because of toxicity. In the secondary hypothesis-generating analyses, patients with reduced UGT1A1 activity had an increased incidence of increased aspartate aminotransferase/alanine aminotransferase (44 vs. 25%; P  = 0.034) and hypertension (52 vs. 31%; P  = 0.024). In addition, patients with increased CYP1A2 activity from carrying CYP1A2*1F had a lower incidence of severe toxicity from pazopanib ( β -coefficient = -0.163, 95% confidence interval: -0.19 to -0.14, P  = 0.008). Future investigations are needed to confirm these associations and determine whether personalized TKI treatment can optimize therapeutic outcomes in patients with cancer.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"295-300"},"PeriodicalIF":1.6,"publicationDate":"2026-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148654138","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":"Distribution of the J1 haplotype variant rs2267439 across CYP2D6 diplotypes and its impact on risperidone metabolism.","authors":"Antonio Asensi Canto, Wendy Y Wang, Erin C Boone, Brandon Retke, Paul Toren, Byunggil Yoo, Oyinlade Kehinde, Samuel E Vaughn, Ogochukwu Amaeze, Akinyemi Oni-Orisan, Andrea Gaedigk, Laura B Ramsey","doi":"10.1097/FPC.0000000000000623","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000623","url":null,"abstract":"<p><p>CYP2D6 is a highly polymorphic pharmacogene responsible for the metabolism of more than 20% of commonly prescribed drugs. Clinical implementation of CYP2D6 pharmacogenetics relies on star allele nomenclature and the Activity Score system, yet substantial interindividual variability in drug exposure remains unexplained. A recent study proposed that the so-called J1 haplotype, defined by rs2267439 C>T located 285 kb downstream of CYP2D6, improves phenotype prediction when combined with revised activity values for selected alleles. However, accurate resolution of the phase of the J1 variant with star alleles requires long-read sequencing due to the distant genomic location of rs2267439 from the gene. In this study, we used phased long-read sequencing data from 884 pediatric subjects to characterize the distribution of the J1-defining variant across CYP2D6 star alleles. Additionally, we evaluated the functional impact of the variants defining the J1, L, and O1 unphased haplotypes on risperidone metabolism in a Nigerian cohort of 125 patients treated with risperidone using targeted genotyping. Phased long-read sequencing revealed that the J1/rs2267439 variant is broadly distributed across CYP2D6 star alleles of all functional categories (normal, decreased, and no function) without preferential co-segregation with any specific allele. In the risperidone-treated African unphased cohort, J1, L, and O1-defining variants were highly prevalent, yet none were associated with statistically significant differences in risperidone metabolic ratios across CYP2D6*1/*1, *1/*2, or *1/*29 diplotype groups. These findings suggest that testing the J1, L, and O1-defining variants may not improve CYP2D6-based phenotype prediction for risperidone. Incorporation of these variants into clinical guidelines requires further validation across diverse populations and multiple substrates.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128333","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":"Pharmacogenetics of inhaled corticosteroids in obesity-related childhood asthma.","authors":"Manaswitha Khare, Shraddha Piparia, Avriti Khare, Scott Weiss, Kelan Tantisira","doi":"10.1097/FPC.0000000000000624","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000624","url":null,"abstract":"<p><p>Asthma is a multifactorial disease driven by genetic and environmental factors that influence pathogenesis and therapeutic response. Obesity and asthma share overlapping inflammatory pathways that worsen disease severity and impair medication response. Inhaled corticosteroids (ICS) are the cornerstone of long-term persistent asthma management, yet 25-30% of patients exhibit poor response. Genetic variants in the T, GLCCI1, and CRHR1 genes have been associated with differential ICS response; however, whether obesity modifies these pharmacogenetic relationships remains unexplored. We conducted a candidate gene analysis in the Caucasian Childhood Asthma Management Program cohort to examine whether obesity status (BMI > 95th percentile; obesity: n = 24, no obesity: n = 176) modifies pharmacogenetic associations with ICS response. The primary outcome was the 2-month change in forced expiratory volume in the first second percentage predicted (FEV1PP) following ICS treatment, evaluated for single-nucleotide polymorphisms (SNPs) rs6456042, rs37972, and rs242941. The overall cohort demonstrated a 5.7% improvement in FEV1PP (P = 0.003). The no-obesity group showed a 6.6% increase (P = 0.001), while the obesity group experienced a -6.2% change (P = 0.26). Significant pharmacogenetic associations with ICS response were identified in the no-obesity group, whereas the obesity group exhibited attenuated or reversed effects for all three SNPs, most notably rs37972.These findings demonstrate for the first time that established pharmacogenetic associations with ICS response are differentially expressed by obesity status. Obesity acts as a pharmacogenetic modifier and likely represents a distinct asthma endotype with unique genetic determinants of ICS response. Endotype-based stratification incorporating obesity is a necessary step toward precision pharmacogenomics in asthma and warrants dedicated pharmacogenomic investigation.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149128302","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 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}