Pharmacogenomics最新文献

{"title":"Pharmacogenomics of cancer therapy-related cardiomyopathy in childhood cancer survivors.","authors":"Suresh Poudel, Yadav Sapkota","doi":"10.1080/14622416.2026.2732153","DOIUrl":"10.1080/14622416.2026.2732153","url":null,"abstract":"<p><p>Cancer therapy-related cardiomyopathy (CTR-cardiomyopathy) is the leading noncancer late effect contributing to morbidity and mortality among adult survivors of childhood cancer. Anthracycline chemotherapy and thoracic radiotherapy are the primary treatment-related risk factors. However, substantial variability among similarly treated individuals highlights the role of germline genetic susceptibility. This review summarizes pharmacogenomic evidence for CTR-cardiomyopathy and the integration of genetic and clinical risk factors for individualized risk prediction. We searched PubMed through July 2026 for studies examining the molecular underpinnings and risk prediction in these survivors. Candidate gene studies identified associations across pathways involved in drug transport (<i>ABCC1</i>, <i>ABCC2</i>, <i>SLC28A3</i>), metabolism (<i>CBR3</i>), oxidative stress (<i>SOD2</i>, <i>CYBA</i>, <i>NCF4</i>), DNA damage response (<i>RARG</i>, <i>XRCC5</i>, <i>MGMT</i>), and inflammation (<i>P2RX</i>7). Genome-wide studies have identified additional loci, including HAS3, ancestry-specific signals (<i>PHTF1/MAGI3</i>, <i>AGBL1</i>), and a doxorubicin-specific locus (<i>KCNK17</i>). Despite progress, barriers to clinical implementation remain, including heterogeneous phenotype definitions, limited replication, especially in non-European populations, and lack of prospectively validated risk models. Integration of multi-omics approaches may improve detection of subclinical cardiac injury. Ultimately, combining polygenic and other omic risk scores with clinical factors and validating these models prospectively across diverse populations will be essential for advancing precision survivorship care.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"479-489"},"PeriodicalIF":1.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671431/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-designing a study on perspectives toward pharmacogenomic testing in mental health care among youth and caregivers.","authors":"Sasha Kullman, Grace Pilkey, Mahin Hasan, Nuzhat Tabassum, Rizwan Ahmed, Cara Katz, Laurence Y Katz, Pop-R Youth Advisory Council, Pop-R Parent/Caregiver Advisory Council, Abdullah Al Maruf, Anna M Chudyk","doi":"10.1080/14622416.2026.2716153","DOIUrl":"10.1080/14622416.2026.2716153","url":null,"abstract":"<p><strong>Aims: </strong>Finding suitable psychotropic medications can be a lengthy trial-and-error process, leading to poor symptom control, low adherence, and treatment failure. Pharmacogenomic (PGx) testing can help inform prescribing considerations for some individuals. As PGx becomes more common in Canada, understanding patients' and families' hopes, expectations, and concerns is vital.</p><p><strong>Materials and methods: </strong>This article details our work engaging two advisory councils comprised of five youth with lived/living experience of mental health challenges and five caregivers across four videoconferencing sessions (between June 2025 and February 2026) aimed at co-designing a qualitative study on perceptions of PGx testing for psychotropic medication prescribing among youth and caregivers. Verbal and written input was gathered from council members and incorporated using iterative feedback cycles.</p><p><strong>Results: </strong>The advisory councils challenged our assumptions and ensured the study design aligned with their lived-experience perspectives. Some suggestions differed between youth and caregiver advisors. Impacts included changes to eligibility criteria, flexible participation options to promote accessibility, and the use of inclusive language in study materials.</p><p><strong>Conclusions: </strong>We recommend that future PGx research actively involves those with lived/living experience to ensure the field is shaped by those it aims to serve.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"365-376"},"PeriodicalIF":1.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671439/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148763304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and psychometric validation of the pharmacogenetic Knowledge, attitudes, and Awareness scale (P-KAAS): an initial validation study in undergraduate nursing students.","authors":"Sukriye Yesilot, Hatice Ceylan, Cansu Kosar Sahin, Cigdem Aydin Acar","doi":"10.1080/14622416.2026.2729994","DOIUrl":"10.1080/14622416.2026.2729994","url":null,"abstract":"<p><strong>Aim: </strong>Pharmacogenetics is a key component of precision medicine, yet its integration into clinical practice remains limited. This study aimed to develop and validate the Pharmacogenetic Knowledge, Attitudes and Awareness Scale (P-KAAS) and assess nursing students' pharmacogenetic competencies.</p><p><strong>Methods: </strong>This methodological, cross-sectional scale-development study included 312 undergraduate nursing students. Content validity was evaluated by an expert panel using the Davis technique. Construct validity was assessed using exploratory factor analysis (EFA) and known-groups validity analyses. Internal consistency, item-total correlations, and test-retest reliability were examined.</p><p><strong>Results: </strong>Students demonstrated moderate awareness and positive attitudes toward pharmacogenetics but limited detailed knowledge. EFA identified a two-factor structure explaining 60.99% of the total variance, with factor loadings ranging from 0.438 to 0.725. Known-groups validity analyses demonstrated significant differences in P-KAAS scores according to academic year and prior exposure to pharmacogenetics. Cronbach's alpha was 0.929 for the total scale, 0.696 for the Knowledge subscale, and 0.938 for the Attitude and Awareness subscale. Test-retest correlations ranged from 0.87 to 0.90.</p><p><strong>Conclusions: </strong>The P-KAAS demonstrated satisfactory psychometric properties among undergraduate nursing students. Further validation in other healthcare professional groups is warranted before broader application.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"405-413"},"PeriodicalIF":1.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671451/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920621","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of <i>SLCO</i> gene polymorphisms with perampanel response and plasma concentrations in patients: a longitudinal retrospective real-world study in refractory epilepsy.","authors":"Ting Zhao, Hong-Jian Li, Hui-Lan Zhang, Jing Yu, Yan Sun, Lu-Hai Yu, Lu-Feng Cheng","doi":"10.1080/14622416.2026.2730713","DOIUrl":"10.1080/14622416.2026.2730713","url":null,"abstract":"<p><strong>Objective: </strong>This study analyzed the correlation between <i>SLCO</i> gene polymorphisms and the efficacy and plasma concentrations of perampanel (PER) in pediatric patients with refractory epilepsy (RE).</p><p><strong>Methods: </strong><i>SLCO</i> genotypes were detected using first-generation Sanger sequencing, and the plasma concentration of PER was measured using ultra-performance liquid chromatography-tandem mass spectrometry.</p><p><strong>Results: </strong>The overall efficacy of PER in treating patients with RE was observed in 64.3% of patients (74 of 115). <i>SLCO1A2</i> rs4149000, <i>SLCO1B1</i> rs2306283, and rs12422149 gene polymorphisms were significantly associated with the efficacy of PER in treating RE. Age, epilepsy duration, concomitant medications, and <i>SLCO1A2</i> rs4149000 polymorphisms were important predictors of effective seizure control related to PER treatment (<i>p</i> < 0.05). PER plasma concentrations were significantly higher in the effective group of pediatric patients receiving the once-daily regimen than in the ineffective group (598.5 ± 390.2 vs 452.9 ± 296.5 ng/mL; <i>p</i> = 0.027).</p><p><strong>Conclusion: </strong><i>SLCO</i> gene polymorphisms were shown to be important predictors of effective seizure control related to PER treatment and were identified as factors affecting plasma concentrations of PER. The findings on <i>SLCO</i> genotypes and PER plasma concentration monitoring provide a promising treatment strategy for Chinese patients with RE.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"395-404"},"PeriodicalIF":1.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149070029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of <i>OPRM1 A118G</i> polymorphism in tramadol analgesia following third molar surgery: a pharmacogenomic study.","authors":"Sourabh Dalvi, Sumita Halder, Rajarshi Kar, Harpreet Grewal, Rachna Gupta, Edelbert Anthonio Almeida, Geetanjali Arora","doi":"10.1080/14622416.2026.2729995","DOIUrl":"10.1080/14622416.2026.2729995","url":null,"abstract":"<p><strong>Background: </strong>The <b><i>OPRM1 A118G (rs1799971)</i></b> polymorphism has been implicated in interindividual variability in opioid analgesic response, but its influence on tramadol efficacy remains uncertain. This study evaluated the association between <i>OPRM1 A118G</i> and postoperative analgesic response to tramadol following mandibular third molar surgery.</p><p><strong>Methods: </strong>In this prospective pharmacogenomic study, 53 adults undergoing impacted mandibular third molar extraction were enrolled. Genomic DNA was analyzed for <i><b>OPRM1 A118G</b></i> <b><i>(rs1799971)</i></b> using amplification refractory mutation system polymerase chain reaction (ARMS-PCR). All procedures were performed under 2% lignocaine with adrenaline. Tramadol (50 mg) was administered after the onset of postoperative pain. Pain intensity was assessed using the Visual Analogue Scale (VAS) and Short-Form McGill Pain Questionnaire at 2, 4, and 6 hours. The primary outcome was summed pain intensity difference (SPID, 2-6 hours).</p><p><strong>Results: </strong>Genotype frequencies were in Hardy-Weinberg equilibrium. No significant association was observed between <i><b>OPRM1</b></i> genotype and SPID, VAS reduction, Pain Rating Index change, or responder status during the 6-hour observation period (all <i>p</i> > 0.05).</p><p><strong>Conclusion: </strong><i>OPRM1 A118G</i> was not significantly associated with early tramadol analgesic response following third molar surgery. <b>Larger studies incorporating both <i>OPRM1</i> and <i>CYP2D6</i> genotyping are needed to clarify the genetic determinants of tramadol analgesia as CYP2D6 gene is required for tramadol metabolism.</b></p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"423-430"},"PeriodicalIF":1.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13671437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148945383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polygenic risk score and risk of drug-induced liver injury after initiating antiretroviral therapy in people living with HIV.","authors":"Zinhle Cindi, Katie M Cardone, Yuki Bradford, Molly A Hall, Hannah Kim, Eric S Daar, Roy Gulick, Sharon A Riddler, Marijana Vujkovic, Kyong-Mi Chang, Philip S Tsao, Phumla Sinxadi, David W Haas, Marylyn D Ritchie","doi":"10.1080/14622416.2026.2698921","DOIUrl":"10.1080/14622416.2026.2698921","url":null,"abstract":"<p><strong>Introduction: </strong>Drug-induced liver injury affects some people living with HIV (PWH) during antiretroviral therapy (ART). We examined associations of polygenic risk scores (PRS) with liver injury during ART.</p><p><strong>Methods: </strong>We derived PRS using summary statistics from the Veterans Affairs Million Veteran Program (MVP) and the Penn Medicine BioBank (PMBB). We constructed PRS for individuals of African (AFR) and European (EUR) ancestry in 3,619 treatment-naïve participants from ART-naive studies of the Advancing Clinical Therapeutics Globally (ACTG) network. Liver injury was defined as incident grade 3 or greater alanine aminotransferase (ALT) within 48 weeks. Associations were evaluated by multivariable regression models.</p><p><strong>Results: </strong>Clinical variables associated with higher baseline ALT values included hepatitis B or C virus infection, increasing BMI and age, and male sex. In analyses of liver injury among 1,897 EUR participants (28 cases, 1869 controls) and 1722 AFR participants (21 cases, 1701 controls), HBV was associated with liver injury in both EUR and AFR participants, and HCV in EUR participants (<i>p</i> < 0.001 for each). PRS_ALT was not independently associated with incident liver injury in either EUR or AFR participants.</p><p><strong>Conclusion: </strong>No association was observed between baseline PRS_ALT and subsequent liver injury following initiation of ART.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"293-303"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148550082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"U.S. student pharmacists perspectives on the pharmacogenomics of escitalopram and aripiprazole.","authors":"Brock Beins, Hans Salcedo, Gloria Grice, Cyrielle Billon","doi":"10.1080/14622416.2026.2710850","DOIUrl":"10.1080/14622416.2026.2710850","url":null,"abstract":"<p><p>Major depressive disorder (MDD) remains a significant illness worldwide, yet antidepressant therapy often follows an empirical \"trial-and-error\" approach. Escitalopram, a selective serotonin reuptake inhibitor is approved for MDD and generalized anxiety disorders, while aripiprazole (ARI), an atypical antipsychotic, is used as adjunctive therapy in treatment-resistant depression. Despite the broad availability of these agents, outcomes remain suboptimal. Data from the STAR*D trial indicate that only one-third of patients achieve remission after their first antidepressant trial, with many requiring multiple adjustments. This reactive approach prolongs symptom burden, increases adverse effects, and delays effective treatment.Advances in pharmacogenomics now offer a means to individualize therapy by identifying genetic polymorphisms - such as those found in CYP2C19 and CYP2D6-that influence escitalopram and aripiprazole metabolism and response. This literature review examines the evidence linking pharmacogenomic variability to antidepressant outcomes and explores how implementing genetic-guided prescribing can improve efficacy, reduce adverse effects, and enhance the pharmacists' role in mental health care.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"345-350"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148664329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of NAT2 acetylation phenotype on toxicity in tuberculosis therapy: a systematic review and meta-analysis.","authors":"Sofia Dinegro, Sara Dal Molin, Ilaria Mariani, Giulia Mosini, Marco Schiuma, Alessandro Torre, Agostino Riva, Andrea Gori, Emilio Clementi, Sonia Radice, Stefania Cheli","doi":"10.1080/14622416.2026.2710853","DOIUrl":"10.1080/14622416.2026.2710853","url":null,"abstract":"<p><strong>Introduction: </strong>Adverse drug reactions (ADRs) remain a major challenge in tuberculosis treatment and frequently compromise therapeutic adherence and outcomes. Hepatotoxicity represents the most clinically significant toxicity. Genetic variability in N‑acetyltransferase 2 (NAT2), the key enzyme involved in isoniazid metabolism, has been associated with toxicity risk, although findings across studies and populations remain heterogeneous.</p><p><strong>Methods: </strong>We conducted a systematic review and random-effects meta-analysis to evaluate the association between <i>NAT2</i> acetylation phenotype and ADRs during tuberculosis treatment. Literature searches were performed across major databases up to September 2025. Geographical variability was assessed by region‑based stratification, while potential methodological and clinical sources of heterogeneity using meta‑regression analyses.</p><p><strong>Results: </strong>Sixty-seven studies, including nearly 14 000 individuals from diverse regions, were analyzed. Slow acetylators showed a significant increased risk of anti‑tuberculosis drug‑induced hepatotoxicity (ATDH) compared with rapid or intermediate acetylators (OR 3.14, 95% CI 2.64-3.74), with a consistent direction of effect across populations despite moderate heterogeneity. Association with other ADRs was more modest (OR 1.65, 95% CI 1.01-2.67). Meta-regression identified age and study size as heterogeneity contributors. Sensitivity analyses confirmed the robustness of the findings.</p><p><strong>Conclusion: </strong><i>NAT2</i> slow acetylation phenotype is a robust determinant of ATDH risk and supports phenotype‑guided precision therapeutic strategies.</p><p><strong>Protocol registration: </strong>PROSPERO registration number CRD420261297224.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"351-363"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556968/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631343","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of ACE I/D polymorphism with blood pressure response to valsartan-hydrochlorothiazide combination therapy in hypertensive patients from Khyber Pakhtunkhwa, Pakistan.","authors":"Aftab Ullah, Abdur Rahim, Asif Jan, Muhammad Khan, Junaid Iqbal, Mequanente Dagnaw","doi":"10.1080/14622416.2026.2711877","DOIUrl":"10.1080/14622416.2026.2711877","url":null,"abstract":"<p><strong>Background: </strong>Interindividual variability in antihypertensive response may be partly explained by genetic variation. The angiotensin-converting enzyme insertion/deletion polymorphism (ACE I/D; rs1799752) has been associated with variable response to renin-angiotensin-aldosterone system-targeting therapies, but evidence for valsartan-hydrochlorothiazide (Val-HCTZ) combination therapy remains limited, particularly in South Asian populations.</p><p><strong>Methods: </strong>In this multicenter prospective cohort study, 645 hypertensive patients from Khyber Pakhtunkhwa, Pakistan, receiving fixed-dose Val-HCTZ were enrolled; 627 were included in the final analysis after excluding 18 patients with poor adherence (<80%) followed for 3 months. ACE I/D genotyping was performed by polymerase chain reaction with confirmatory testing. The primary analysis evaluated blood pressure reduction across ACE I/D genotypes using regression models adjusted for age, sex, and body mass index. Achievement of target blood pressure (<140/90 mmHg) was analyzed as a secondary outcome.</p><p><strong>Results: </strong>Genotype distribution was in Hardy-Weinberg equilibrium (<i>p</i> = 0.171). Blood pressure reduction differed across genotypes, with the most favorable response observed in DD carriers, an intermediate response in II carriers, and the least favorable response in ID carriers. In the primary analysis of continuous blood pressure reduction, ID carriers showed significantly less reduction compared to II carriers (ΔSBP: adjusted β = -11.2, 95% CI: -16.8 to -5.6, <i>p</i> = 0.002; ΔDBP: adjusted β = -7.4, 95% CI: -11.9 to -2.9, <i>p</i> = 0.004). DD carriers showed greater observed reduction compared to II carriers, but this was not statistically significant (ΔSBP: adjusted β =  +1.8, 95% CI: -4.2 to +7.8, <i>p</i> = 0.561; ΔDBP: adjusted β =  +0.5, 95% CI: -4.1 to +5.1, <i>p</i> = 0.823). In the secondary analysis, response rates were 90.6% for DD, 75.8% for II, and 40.8% for ID.</p><p><strong>Conclusion: </strong>ACE I/D genotype was associated with variation in blood pressure response to fixed-dose Val-HCTZ therapy in this Pakistani cohort, with the most robust finding being poorer response among ID carriers. These findings support further investigation of ACE I/D as a candidate pharmacogenetic marker in genotype-stratified and interventional studies.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"317-324"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556926/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148631302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of dopamine transporter gene variations in Turkish children with attention deficit hyperactivity disorder treated with methylphenidate adverse effects.","authors":"Kubra Cigdem Pekkoc-Uyanik, Melik Yigit Bayindir, Muhammet Fatih Akdemir, Aybike Aydin Okuyan, Mahmut Cem Tarakcioglu, Sibel Ozyazgan, Zeynep Gizem Todurga Seven","doi":"10.1080/14622416.2026.2706504","DOIUrl":"10.1080/14622416.2026.2706504","url":null,"abstract":"<p><strong>Aim: </strong>Attention-deficit hyperactivity disorder (ADHD) is a common childhood psychiatric disorder, with methylphenidate (MPH) as the first-line treatment. MPH primarily exerts its effects by inhibiting the dopamine transporter (DAT); therefore, variants in the <i>DAT1</i> gene may affect susceptibility to its adverse effects.</p><p><strong>Methods: </strong>This study included 47 children and adolescents diagnosed with ADHD according to DSM-5-TR criteria who were receiving MPH treatment. MPH-related adverse effects were assessed using the Barkley Stimulants Side Effects Rating Scale. Participants were categorized into groups based on whether they experienced adverse effects. The exons of the <i>DAT1</i> gene were sequenced using NGS.</p><p><strong>Results: </strong>A total of 16 variants were identified in the <i>DAT1</i> gene, including intronic, untranslated region, synonymous, splice-region, and splice polypyrimidine tract variants. One rare intronic deletion variant, c.1032-44_1032-42del, was classified as a VUS. Genetic association analyses identified significant associations for rs1042098 under the genotypic (<i>p</i> = 0.003; BH q = 0.019) and dominant (<i>p</i> = 0.037; BH q = 0.091) models, and for rs6876890 under the genotypic model (<i>p</i> = 0.008; BH q = 0.044).</p><p><strong>Conclusions: </strong>Our findings suggest that specific <i>DAT1</i> gene polymorphisms, particularly rs1042098 and rs6876890, may be associated with MPH-related adverse effects in children and adolescents with ADHD.</p>","PeriodicalId":20018,"journal":{"name":"Pharmacogenomics","volume":" ","pages":"305-315"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556950/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}