Pharmacogenetics and genomics最新文献

{"title":"Haplotype-based association of HTR2A rs6311-rs6313 with early risperidone-clozapine response in Batak patients with schizophrenia.","authors":"Nurul Hidayah, Muthi Ikawati, Mustafa Mahmud Amin, Zullies Ikawati","doi":"10.1097/FPC.0000000000000620","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000620","url":null,"abstract":"<p><strong>Background: </strong>Risperidone-clozapine response varies substantially in schizophrenia. HTR2A polymorphisms may influence antipsychotic response, but rs6311-rs6313 haplotypes remain unexplored in the Indonesian Batak population. This study evaluated associations of HTR2A rs6311-rs6313 with early risperidone-clozapine response.</p><p><strong>Methods: </strong>This prospective observational case-control study included 160 Batak inpatients with schizophrenia, comprising 80 responders and 80 nonresponders to risperidone-clozapine therapy. Genetic analyses included Hardy-Weinberg equilibrium (HWE), minor allele frequency (MAF), linkage disequilibrium, genotype and allele association, haplotype, permutation testing, genetic models, and multivariable logistic regression.</p><p><strong>Results: </strong>Genotype distributions conformed to HWE (P > 0.05), with both variants showing a MAF of 0.28 and strong linkage disequilibrium (r2 = 0.969, D' = 0.98). The rs6311 GG/rs6313 CC genotype was significantly associated with nonresponse to risperidone-clozapine therapy [odds ratio (OR) = 3.69, 95% confidence interval (CI): 1.10-12.36; P = 0.034], while the rs6311 G/rs6313 C allele was also associated with nonresponse (OR = 1.71, 95% CI: 1.04-2.80; P = 0.034). The recessive model remained significant after multivariable adjustment (adjusted OR = 3.36, 95% CI: 1.02-11.07; P = 0.046). TA and CG haplotypes remained significant after 10 000 permutations (P = 0.0415 and P = 0.0416), whereas single-marker associations lost significance (P = 0.0607).</p><p><strong>Conclusion: </strong>HTR2A variation was associated with early risperidone-clozapine response, with consistent signals under the recessive model and at the haplotype level. Haplotype associations remained significant after permutation correction, suggesting that haplotype analysis may provide a more robust approach for detecting pharmacogenetic contributions to treatment response.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":""},"PeriodicalIF":1.6,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148860616","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":"https://doi.org/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":""},"PeriodicalIF":1.6,"publicationDate":"2026-08-04","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":"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":"https://doi.org/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":""},"PeriodicalIF":1.6,"publicationDate":"2026-07-28","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":"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":"https://doi.org/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":""},"PeriodicalIF":1.6,"publicationDate":"2026-07-10","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":"CFTR genotype-phenotype associations and clinical outcomes in pediatric cystic fibrosis.","authors":"Luana da Silva Baptista Arpini, Fernanda Mayrink Gonçalves Liberato, Sabrina da Silva Santos, Gina Torres Rego Monteiro","doi":"10.1097/FPC.0000000000000601","DOIUrl":"10.1097/FPC.0000000000000601","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the association between CFTR genotypes and clinical and nutritional outcomes in children and adolescents with cystic fibrosis (CF) receiving care within the public health system of Espírito Santo, Brazil.</p><p><strong>Methods: </strong>This cross-sectional study retrospectively analyzed clinical and genetic data from 110 individuals under 18 years with confirmed CF, followed at a state reference center between 2007 and 2024. CFTR variants were classified by functional consequence and grouped by severity. Outcomes included pancreatic insufficiency, forced expiratory volume in 1 s (FEV1%), Shwachman-Kulczycki score, nutritional status, and chronic airway colonization by Pseudomonas aeruginosa . Associations were assessed using appropriate statistical tests.</p><p><strong>Results: </strong>A high degree of CFTR genotypic heterogeneity was observed, with predominance of the F508del variant (72.7%) alongside a substantial proportion of non-F508del and rare pathogenic variants. Individuals carrying two class I-III variants had a higher frequency of pancreatic insufficiency ( P = 0.026). The presence of p.Phe508del was associated with worse pulmonary function ( P = 0.031) and bone demineralization ( P = 0.026). The Shwachman-Kulczycki score correlated negatively with age and age at diagnosis and positively with BMI z -score and FEV1%. No significant associations were found between genotype and chronic P. aeruginosa colonization, liver disease, or overall disease severity.</p><p><strong>Conclusion: </strong>CFTR genotypic heterogeneity was high, with minimal function variants associated with poorer clinical outcomes. The notable presence of rare variants underscores the need for regional studies to better characterize phenotypic variability and support precision medicine strategies in middle-income settings.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"163-170"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147777831","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":"TWSG1 variation identifies a ustekinumab-response phenotype in patients with inflammatory bowel disease.","authors":"Mohammed Alkhalifa, Gio R Dela Cruz, Terry Ponich, James C Gregor, Brian Yan, Reena Khanna, Keith McIntosh, Melanie D Beaton, Richard B Kim, Aze Wilson","doi":"10.1097/FPC.0000000000000602","DOIUrl":"10.1097/FPC.0000000000000602","url":null,"abstract":"<p><strong>Objectives: </strong>A genome-wide association study identified that genetic variation in the twisted gastrulation protein homolog-1 gene ( TWSG1 rs7242593) was linked to early clinical remission in ustekinumab-exposed patients in the UNITI clinical trials. We aimed to confirm if a single nucleotide variation (SNV) in the TWSG1 gene is associated with clinical remission in inflammatory bowel disease (IBD) patients on ustekinumab.</p><p><strong>Methods: </strong>A retrospective cohort study was conducted in ustekinumab-treated IBD patients. Participants underwent screening for the TWSG1 SNV rs7242593 and were assessed for clinical disease remission by Harvey-Bradshaw Index or partial Mayo score at 3 and 12 months. Ustekinumab dose and treatment duration were also assessed.</p><p><strong>Results: </strong>A total of 125 IBD participants were included (wild-type genotype, CC, n  = 108; variant genotype, CT, n  = 17). Participants in the variant genotype group were more likely to achieve clinical remission at 3 months [odds ratio (OR): 23.11, 95% confidence interval (CI) = 3.92-449.40, adjusted P  = 0.0043] and at 12 months (OR = 17.75, 95%CI = 2.42-381.0, adjusted P  = 0.016) on standard ustekinumab dosing and less likely to discontinue therapy during the follow-up period (hazard ratio=4.20, 95% CI = 1.94-9.09, P  = 0.02). For wild-type carriers, ustekinumab dose escalations were not associated with disease remission at any time.</p><p><strong>Conclusion: </strong>TWSG1 SNV was associated with early and persistent clinical remission in ustekinumab-exposed IBD patients. Wild-type carriers who did not achieve remission were not rescued with high-dose treatment.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"157-162"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729646","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":"Characteristics of initial pharmacogenetic testing and subsequent physician referral behavior in youth mental health.","authors":"Naomi Lemboye, Madison Heintz, Abdullah Al Maruf, Sarker M Shaheen, Ryden McCloud, Laina McAusland, Paul D Arnold, Chad A Bousman","doi":"10.1097/FPC.0000000000000603","DOIUrl":"10.1097/FPC.0000000000000603","url":null,"abstract":"<p><p>While prior studies have focused on the clinical utility of pharmacogenetic (PGx) testing, less is known about factors that influence physicians' continued use of PGx testing in routine practice. Using data from the PGx-SParK trial, we examined whether the actionability of PGx test results from a physician's initial referral predicted subsequent PGx referral behavior. Youth aged 6-24 years referred for PGx testing in Western Canada between October 2020 and November 2025 were included. For each physician, an index PGx referral was identified and linked to patient characteristics, testing turnaround time, and CYP2B6, CYP2C19, and CYP2D6 results. Actionability for psychotropic prescribing was defined based on current PGx guidelines and categorized as current, future, or none. The number of subsequent referrals per physician was modeled using generalized linear models with a Poisson distribution corrected for overdispersion and adjusted for follow-up time and relevant covariates. Among 371 physician index referrals, 90% of tested youth had at least one current (22%) or future (68%) actionable result. Over a mean follow-up of 29 months, 52% of physicians made at least one subsequent PGx referral. Neither current nor future actionability of the initial PGx test results was associated with subsequent referral behavior. However, patient age (older) and physician speciality (psychiatrists) were associated with greater odds of a subsequent referral. These findings suggest that sustained physician engagement with PGx testing in youth mental healthcare may be driven more by implementation context and physician-level factors than by the clinical actionability of test results.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"171-175"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729654","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 TPMT and NUDT15 diplotypes in Mexican children with B-cell acute lymphoblastic leukemia.","authors":"Joaquin Garcia-Solorio, Carolina Molina-Garay, Víctor Jesús Sánchez-Martínez, Beatriz Eugenia Villegas-Torres, Irlanda Campos-Perez, Marco Jiménez-Olivares, Fernanda Flores-Espino, Diana Casique-Aguirre, Juan Carlos Núñez-Enriquez, Janet Flores-Lujano, Minerva Mata-Rocha, José Gabriel Peñaloza-Gonzalez, Victor Hugo Olivares-Villalpando, Ma Del Rocío Baños-Lara, Ángel García-Soto, César Alejandro Galván-Díaz, Alberto Olaya-Vargas, Moises Solano-Cardozo, Miguel Ángel Garrido-Hernández, Nuria Citlalli Luna-Silva, Lena Sarahi Cano-Cuapio, Karol Carrillo-Sanchez, Luis Leonardo Flores-Lagunes, Elvia Cristina Mendoza-Caamal, Vincent González-Osnaya, Rosana Pelayo-Camacho, Juan Manuel Mejía-Arangure, Jun J Yang, Carmen Alaez-Verson","doi":"10.1097/FPC.0000000000000593","DOIUrl":"10.1097/FPC.0000000000000593","url":null,"abstract":"<p><strong>Objective: </strong>To characterize the allelic and diplotype variability of TPMT and NUDT15 in pediatric patients with B-cell acute lymphoblastic leukemia from the central-southern region of Mexico.</p><p><strong>Methods: </strong>Samples from 275 pediatric B-cell acute lymphoblastic leukemia patients were analyzed. Next-generation sequencing was used for TPMT and NUDT15 genotyping. Alleles and diplotypes were assessed according to the Clinical Pharmacogenetics Implementation Consortium guidelines. Their geographic distribution was compared across Mexican states and global populations. In-silico analyses were conducted to assess the structural and functional impact of TPMT variants not associated with star alleles.</p><p><strong>Results: </strong>The wild-type *1 allele, associated with normal enzymatic activity, was predominant in both genes: TPMT (94.15%) and NUDT15 (90.45%). TPMT showed greater allelic diversity compared with previous studies in Mexican populations. Alleles conferring absent or indeterminate enzymatic activity in TPMT were distributed across six diplotypes (11.62%), with *3A allele (4.73%) and *1 / *3A diplotype (9.45%) being the most frequent. Additionally, two unclassified TPMT variants, p.G126A and p.D137Y, were identified. For NUDT15 , three non-wild-type diplotypes were observed (19.09%), with the *2 allele (6.74%) and *1* / 2 diplotype (13.48%) being the most prevalent.</p><p><strong>Conclusion: </strong>Approximately 28% of patients carried TPMT and/or NUDT15 variants associated with non-wild-type enzymatic activity, increasing the risk of mercaptopurine-induced myelotoxicity. Preemptive genotyping is essential to reduce toxicity, optimize treatment, and advance precision medicine in this population. Additionally, the two TPMT variants p.G126A and p.D137Y, currently not classified within Clinical Pharmacogenetics Implementation Consortium-defined star alleles, highlight the need for functional validation and potential clinical classification to improve pharmacogenetic interpretation in diverse populations.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"143-150"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146106679","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":"Application of risk priority number of failure mode and effects analysis to drug-variant pairs for severe cutaneous adverse reactions in Korean and American populations.","authors":"Hyun Kyung Lee, Min Ju Kang, Hajung Kim, Ha Young Jang, Nayoung Han, In-Wha Kim, Jung Mi Oh","doi":"10.1097/FPC.0000000000000596","DOIUrl":"10.1097/FPC.0000000000000596","url":null,"abstract":"<p><strong>Objectives: </strong>Given the varying frequency and significance of genetic factors associated with severe cutaneous adverse reactions (SCARs) across different ethnicities, this study aimed to identify high-risk priority drug-variant pairs by considering genetic differences between Korea and the USA to inform preventive strategies.</p><p><strong>Methods: </strong>A list of drug-variant pairs associated with SCARs was identified using the Pharmacogenomics Knowledge Base. Prioritization of drug-variant pairs for preventive strategies was conducted using the risk priority number (RPN) method incorporating expert opinions in the field of drug allergy. The RPN for each drug-variant was calculated based on severity, probability, and detectability, with each parameter derived as an odds ratio of the genetic variant associated with SCARs, the occurrence frequency of drug-associated SCARs, and the variant prevalence in Korean and American populations, respectively. Higher values were evaluated as higher priority.</p><p><strong>Results: </strong>A total of 80 drug-variant pairs from 16 drugs associated with SCARs were identified in Koreans, and 12 drug-variant pairs from four drugs in Americans. Six drug-variant pairs were included in Korean drug labels, while only two drug-variant pairs were included in US drug labels. In Koreans, the highest priority drug-variant pair was rs3131003 for allopurinol, which is in moderate linkage disequilibrium with HLA-B*58:01 , whereas in Americans, HLA-B*58:01 itself for allopurinol was the highest priority variant.</p><p><strong>Conclusion: </strong>Drug-variant pairs with high RPN scores can be prioritized in clinical strategies to prevent SCARs in Korean and American populations. Incorporating these findings into clinical practices could ultimately contribute to the safe use of drugs.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"125-133"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147474924","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":"Effects of apolipoprotein E and solute carrier organic anion transporter family member 1B1 gene polymorphisms on statin efficacy and safety in dyslipidemic patients.","authors":"Xiaohong Wu, Yumei Cai, Yonglong Su, Xianni Wei, Tingting Nan, Xiaoyun Ye, Siheng Lian, Jinbao Wei","doi":"10.1097/FPC.0000000000000598","DOIUrl":"10.1097/FPC.0000000000000598","url":null,"abstract":"<p><strong>Objective: </strong>To investigate the distribution of the apolipoprotein E ( ApoE ) and solute carrier organic anion transporter family member 1B1 ( SLCO1B1 ) polymorphisms in dyslipidemia patients and their impact on statin efficacy and safety.</p><p><strong>Methods: </strong>A retrospective analysis was conducted on dyslipidemic inpatients (April 2024-March 2025) who received statin therapy and genetic testing for SLCO1B1 (rs4149056) and ApoE (rs429358 and rs7412), to analyze the association of genotypes with lipid levels and safety indicators.</p><p><strong>Results: </strong>The final analysis included 238 hospitalized patients with dyslipidemia (156 males and 82 females) who met the inclusion criteria. The study population had a mean age of 60.61 ± 0.91 years (mean ± SEM). The allele frequencies for both ApoE and SLCO1B1 polymorphisms were in Hardy-Weinberg equilibrium ( P  > 0.05). Analysis of statin efficacy revealed a significant association between ApoE genotype and atorvastatin response: E3 carriers demonstrated higher low-density lipoprotein cholesterol levels posttreatment compared to E2 carriers (2.85 ± 1.00 mmol/l vs. 2.28 ± 0.96 mmol/l, P  = 0.026). However, no such association was found in patients administered rosuvastatin. For safety outcomes, comparisons of creatine kinase and alanine aminotransferase levels between carriers of the SLCO1B1 TC and TT genotypes showed no statistically significant differences.</p><p><strong>Conclusion: </strong>APOE polymorphisms influence statin efficacy. The E2 genotype is associated with better atorvastatin efficacy in lipid management. At low-to-moderate doses, the SLCO1B1 TC genotype did not increase safety risk, supporting its clinical safety.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"151-156"},"PeriodicalIF":1.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13200858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147491498","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}