Pharmacogenetics and genomics最新文献

{"title":"UGT1A1 polymorphisms and metabolic phenotypes in indigenous peoples from the Brazilian Amazon.","authors":"Jamila A Perini, Alessandra S Dias, Leonor Gusmão, Larissa B Skaf, Anna Beatriz R Elias, Paulo C Basta, Marcelo A Carvalho, Guilherme Suarez-Kurtz","doi":"10.1097/FPC.0000000000000566","DOIUrl":"10.1097/FPC.0000000000000566","url":null,"abstract":"<p><strong>Objectives: </strong>To explore the distribution of clinically relevant UGT1A1 polymorphisms and inferred UGT1A1 phenotypes in two Indigenous groups (Paiter-Suruí and Yanomami) from reservation areas in the Brazilian Amazon.</p><p><strong>Methods: </strong>Ninety-two Yanomami and 88 Paiter-Suruí were genotyped with a validated panel of ancestry informative markers. Individuals with >90% Native ancestry were genotyped for the promoter TA repeat (rs8175347) polymorphism and UGT1A1*6 (rs4148323) by direct sequencing, and for UGT1A1*80 (rs887829) by TaqMan allele discrimination. The UGT1A1 metabolic phenotypes were inferred from UGT1A1 diplotypes.</p><p><strong>Results: </strong>All Yanomami and 85 (96.6%) Paiter-Suruí had >92% Native ancestry. UGT1A1 genotype data from these individuals revealed: (i) the absence of both alleles with five and eight TA repeats [TA(5) and TA(8)]; (ii) TA(7) allele frequency of 0.470 in Yanomami and 0.441 in Paiter-Suruí; (iii) rs4148323 was absent in Paiter-Suruí and detected in two Yanomami (frequency 0.012); (iv) a perfect linkage disequilibrium (LD) between rs887829C>T and the promoter repeat polymorphisms in both cohorts: C allele with TA(6) and T allele with TA(7). The distribution of the inferred UGT1A1 metabolizer phenotypes did not differ between cohorts (Paiter-Suruí and Yanomami): the intermediate metabolizer was the most common (50.6-55.4%), followed by the normal (30.6-24.1%) and the slow (18.8-20.5%) phenotypes.</p><p><strong>Conclusion: </strong>This is the first report on the frequency distribution of clinically relevant UGT1A1 variants and inferred UGT1A1 metabolic phenotypes in two major Native populations from indigenous reservation areas in the Brazilian Amazon, namely the Paiter-Suruí and Yanomami. The TA(5) and TA(8) repeats were absent, whereas TA(7) was common (frequency >0.50) in both cohorts. The intronic rs887829 variant ( UGT1A1 * 80 ) single nucleotide variant was found in perfect LD with the promoter TA repeats. The rs4148323 SNP was absent (Paiter-Suruí) or rare (Yanomami). The frequency of high-risk UGT1A1 poor metabolizer phenotype was 1.6- to 2-fold higher in the indigenous cohorts compared to nonindigenous Brazilians.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"153-158"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144030661","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":"Assessment of the potential impact of polymorphisms in the Foxp3 and CTLA-4 genes in immune balance and disease susceptibility of primary Sjögren's syndrome.","authors":"Min Feng, Fanxing Meng, Yanlin Wang, Yuhan Jia, Guozhen Ji, Yue Jin, Chong Gao, Jing Luo","doi":"10.1097/FPC.0000000000000567","DOIUrl":"10.1097/FPC.0000000000000567","url":null,"abstract":"<p><strong>Background: </strong>Regulatory T (Treg) cell depletion-associated immune tolerance deficiency have been shown to play a key role in the pathogenesis of primary Sjögren's syndrome (pSS). Treg cells mainly express the transcriptional regulator Foxp3 and are characterized by constitutively high expression of inhibitory coreceptor CTLA-4 . Herein, the aim of this study was to investigate the potential association of single nucleotide polymorphisms (SNPs) in Foxp3 and CTLA-4 genes with the susceptibility to pSS.</p><p><strong>Method: </strong>Ninety-nine pSS patients and 93 healthy controls were recruited into the retrospective study. Nuclear DNA was extracted from peripheral blood leukocytes, and SNP alleles were identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.</p><p><strong>Results: </strong>For the Foxp3 gene, the T allele, the TT and GT genotype in rs3761548G/T, the A allele and AA genotype in rs3761549G/A, as well as the C allele and the TC genotype in rs2280883T/C, were preponderant in pSS. Polymorphisms of rs3761548G/T and rs3761549G/A were found to be associated with anemia or leukopenia, while rs2232365T/C was associated with neutropenia, and rs2280883T/C was demonstrated to have a correlation with anti-SSA(+). For the CTLA-4 gene, the C allele and the CC genotype in rs733618T/C were significantly more prevalent in pSS. rs733618T/C polymorphisms varied significantly in anti-SSA(+), anti-SSB(+) and leukopenia, and rs16840252T/C was associated with ANA(+). Patients with at least six risk alleles had higher Th17 cells and decreased Treg cell counts, accompanied by elevated Th1/Treg, Th2/Treg, and Th17/Treg ratios. And the phenomenon was also observed in patients with four or more variant genotypes.</p><p><strong>Conclusion: </strong>Polymorphisms in Foxp3 and CTLA-4 genes were associated with the susceptibility to pSS. The greater number of mutant sites and variant genotypes an individual possessed, the more susceptible they became to immune dysregulation.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"159-169"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144023027","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":"Impact of switching antiplatelet therapy in acute coronary syndrome patients with different CYP2C19 phenotypes: insights from a single-center study.","authors":"Nagendra Boopathy Senguttuvan, Muralidharan Thoddi Ramamurthy, Nithesh Kumar, Pavitraa Saravana Kumar, Yogapriya Chidambaram, Madhesh Kasi, Gautam Ganesan Karthikeyan, Asuwin Anandaram, Bharath Raj Kidambi, Sadhanandham Shanmugasundram, Manokar Panchanatham, Rammurthy Anjanappa, Venu Seenappa, Vettriselvi Venkatesan, Ramesh Sankaran, Thanikachalam Sadagopan","doi":"10.1097/FPC.0000000000000564","DOIUrl":"10.1097/FPC.0000000000000564","url":null,"abstract":"<p><strong>Objective: </strong>Optimizing antiplatelet therapy is crucial in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary interventions (PCIs). This study aimed to assess the prevalence of CYP2C19 loss-of-function (LOF) variants and evaluate the clinical outcome of ticagrelor, clopidogrel, and aspirin in patients with ACS-PCI.</p><p><strong>Methods: </strong>This study included patients from the southern part of India (predominantly Tamil Nadu) with coronary artery disease and PCI. They were categorized based on their CYP2C19 LOF variants. Patients were further divided into group 1 (continued ticagrelor) and group 2 (switched to clopidogrel) and followed up for 40 months. The primary and secondary outcomes were evaluated.</p><p><strong>Results: </strong>A total of 287 patients were genotyped, 36.2% were normal, 46.3% were intermediate, and 17.5% were poor metabolizers, the predominant allele being CYP2C19 *2. After considering only patients who underwent PCI and received ticagrelor, 111 patients were recruited. Ticagrelor was switched to clopidogrel in 45.9% of patients. No statistically significant differences in major adverse cardiovascular events or individual outcomes were observed among different metabolizer groups and patients switched from ticagrelor to clopidogrel. Intermediate metabolizers (IMs) exhibited a trend favoring ticagrelor continuation. Notably, discontinuation of aspirin in IM was linked to increased target vessel reintervention (TVR) in the clopidogrel-only group.</p><p><strong>Conclusion: </strong>Our study provides preliminary evidence on favoring ticagrelor continuation and increased TVR upon aspirin withdrawal in IM.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"145-152"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670614","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":"Integrating pharmacogenetics in sport medicine: enhancing treatment precision and preventing unintentional doping violation.","authors":"Guillaume Drevin, Marie Briet, Chadi Abbara","doi":"10.1097/FPC.0000000000000565","DOIUrl":"https://doi.org/10.1097/FPC.0000000000000565","url":null,"abstract":"","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"35 5","pages":"170-171"},"PeriodicalIF":1.7,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144151399","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 estrogen and progesterone receptor polymorphisms with idiopathic thin endometrium.","authors":"Belén Lledo, Mónica Hortal, María Martínez, Jose A Ortiz, Ruth Morales, Andrea Bernabeu","doi":"10.1097/FPC.0000000000000560","DOIUrl":"10.1097/FPC.0000000000000560","url":null,"abstract":"<p><p>The research question is as follows: Are estrogen and progesterone receptor genotypes associated with thin endometrium? We performed a prospective cohort study of 129 patients who underwent preimplantation genetic testing for aneuploidies. These patients were categorized according to endometrial thickness: >7 mm control group ( n  = 94) and ≤7 mm study group ( n  = 35). Polymorphisms in the genes ESR1 (rs9340799 and rs3138774), ESR2 (rs1256049 and rs4986938), and PGR (rs1042838) were analyzed. Regarding genotype distribution, the GA/AA genotype frequency for rs4986938- ESR2 was higher in the thin endometrium group (80% in the study group vs. 50% in the control group; P  = 0.002), as well as the GG genotype of PGR (8.6% in the study group vs. 0% in the control group; P  = 0.002). No differences were observed for the remaining genotypes. In terms of clinical data, the pregnancy rate after euploid embryo transfer was lower in patients with the AA genotype for rs4986938- ESR2 (18.2% AA vs. 40.8% GA vs. 44.0% GG; P  = 0.039). Finally, a predictive pregnancy model was developed using clinical data and ESR2 and PGR genotypes, with an area under the curve of 0.76, sensitivity of 64%, and specificity of 76%. The genetic variants rs4986938 in the ESR2 gene and rs1042838 in the PGR gene seem to correlate with idiopathic thin endometrium. In addition, the rs4986938 polymorphism in the ESR2 gene is associated with pregnancy rate. Finally, a predictive model combining clinical data and patient genetic profiles has been proposed to predict clinical pregnancy outcomes.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"136-139"},"PeriodicalIF":1.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060089","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 impact of genetic variations in FPGS , MTHFR , and ATIC on methotrexate response among pediatric patients with acute lymphoblastic leukemia.","authors":"Shu-Mei Wang, Dan-Qi Zhao, Xiao-Yan Kong, Miao Li","doi":"10.1097/FPC.0000000000000563","DOIUrl":"10.1097/FPC.0000000000000563","url":null,"abstract":"<p><strong>Objectives: </strong>Genetic polymorphisms in FPGS , MTHFR , and ATIC have emerged as important modulators of methotrexate (MTX) metabolism and toxicity. We investigated the distribution of FPGS rs10106, MTHFR rs1801131, and ATIC rs2372536 polymorphisms in children with acute lymphoblastic leukemia (ALL) and assessed their influence on MTX concentrations, toxicity profiles, and clinical outcomes.</p><p><strong>Methods: </strong>Genotyping of FPGS rs10106 G > A, MTHFR rs1801131 A > C, and ATIC rs2372536 C > G polymorphisms was conducted using the Sequenom MassARRAY iPLEX platform in 145 pediatric ALL patients.</p><p><strong>Results: </strong>Significant ethnic differences were observed in the allelic and genotypic distributions of the three single nucleotide polymorphisms (SNPs) investigated. None of these three SNPs had a significant effect on MTX levels or toxicities. The frequencies of the ATIC rs2372536 CC genotype and C allele in ALL patients (44.8% and 68.6%, respectively) were significantly lower than those in Han Chinese in Beijing, China (58.3% and 78.2%, respectively; P  = 0.036 and 0.019, respectively). Patients carrying the ATIC rs2372536 GG genotype (36.4%, 4/11) had a significantly higher relapse rate than the CC genotype carriers (6.2%, 4/65, P  = 0.013). There, however, were no significant effects on relapse-free survival in Kaplan-Meier and Cox regression analyses for all three candidate SNPs.</p><p><strong>Conclusion: </strong>Our findings offer valuable insights into the intricate interplay between genetic polymorphisms, MTX exposure, toxicities, and clinical outcomes in patients with ALL and have the potential to inform precision medicine strategies.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"127-135"},"PeriodicalIF":1.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143483736","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 plasma dolutegravir exposure during 1-month rifapentine/isoniazid treatment of latent tuberculosis.","authors":"Nia Covington, Anne F Luetkemeyer, Marjorie Z Imperial, Rodney Dawson, Yoninah Cramer, Sue Rosenkranz, Susan Swindells, Irina Gelmanova, Anchalee Avihingsanon, Roberto C Arduino, Wadzanai Samaneka, Kelly E Dooley, Rada Savic, Anthony T Podany, David W Haas","doi":"10.1097/FPC.0000000000000562","DOIUrl":"10.1097/FPC.0000000000000562","url":null,"abstract":"<p><p>In Advancing Clinical Therapeutics Globally protocol A5372, a pharmacokinetic study of dolutegravir with 1-month of daily rifapentine/isoniazid, twice-daily dolutegravir offset the induction effects of rifapentine on plasma dolutegravir trough concentrations (C trough ). Here, we characterize the impact on dolutegravir C trough of UGT1A1 , AADAC , and NAT2 polymorphisms that affect dolutegravir, rifapentine, and isoniazid, respectively. People with HIV receiving dolutegravir-based antiretroviral therapy with an indication to treat latent tuberculosis underwent pharmacokinetic sampling during dolutegravir 50 mg once daily alone, and on day 28 of dolutegravir 50 mg twice daily with rifapentine/isoniazid. Multivariable linear regression models characterized genetic associations with dolutegravir C trough . Among 30 participants evaluable for genetic associations, median (Q1, Q3) day 0 dolutegravir C trough was 1745 (1099, 2694) ng/ml, and day 28 was 2146 (1412, 2484) ng/ml. Day 28 C trough was higher with UGT1A1 rs887829 TT [geometric mean ratio (GMR) = 1.65; 90% confidence interval (CI): 0.97-2.78] and CT (GMR = 1.38; 90% CI: 1.02-1.86) than with CC, and was higher with AADAC rs1803155 GG (GMR = 1.79; 90% CI: 1.09-2.93) and AG (GMR = 1.48; 90% CI: 1.14-1.90) than with AA. Median day 28 C trough ranged from 1205 (1063, 1897) ng/ml with 4 total UGT1A1 and AADAC risk alleles, to 3882 and 3717 ng/ml with only one risk allele. Individuals with concomitant AADAC slow metabolizer and UGT1A1 normal metabolizer genotypes may be at greater risk for clinically significant drug-drug interactions between rifapentine/isoniazid and dolutegravir.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"140-144"},"PeriodicalIF":1.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143441784","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":"Metabolic effects of heterocyclic amines on insulin‑induced AKT phosphorylation and gluconeogenic gene expression are modified by N -acetyltransferase 2 genetic polymorphism.","authors":"Kennedy M Walls, Jonathan Y Joh, Madeline M Martinez, Kyung U Hong, David W Hein","doi":"10.1097/FPC.0000000000000559","DOIUrl":"10.1097/FPC.0000000000000559","url":null,"abstract":"<p><strong>Objective: </strong>Heterocyclic amines (HCAs) are mutagens and carcinogens primarily generated when cooking meat at high temperatures or until well-done, and their major metabolic pathway includes hepatic N -hydroxylation via CYP1A2 followed by O -acetylation via N -acetyltransferase 2 (NAT2). NAT2 expresses a well-defined genetic polymorphism in humans resulting in rapid and slow acetylators. Recent epidemiological studies reported significant associations between dietary HCA exposure and insulin resistance and type II diabetes.</p><p><strong>Methods: </strong>We assessed the effect of some of the most common HCAs found in cooked meat, 2-amino-3,4-dimethylimidazo[4,5-f]quinoline, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine, on insulin signaling and gluconeogenic gene expression in cryopreserved human hepatocytes characterized by their NAT2 genotype and phenotype to investigate the role of NAT2 genetic polymorphism in HCA-induced metabolic dysregulation.</p><p><strong>Results: </strong>HCA treatment significantly reduced insulin-induced protein kinase B phosphorylation and significantly increased expression of genes involved in gluconeogenesis ( G6PC , PCK1 , FOXO1 , and PPARA ) in cryopreserved human hepatocytes from rapid but not from slow acetylators.</p><p><strong>Conclusion: </strong>The findings suggest that NAT2 genetic polymorphism modifies HCA-induced insulin resistance and gluconeogenic gene expression, implying that individuals with rapid acetylator phenotype may be at greater risk of dysregulated glucose homeostasis following exposure to HCAs.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"119-126"},"PeriodicalIF":1.7,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12043411/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143060008","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":"Updated analysis of the pharmacogenomics of pediatric bronchodilator response.","authors":"Jennifer Brailsford, Guillaume Labilloy, Nolan Menze, Morgan Henson, Jennifer Fishe","doi":"10.1097/FPC.0000000000000557","DOIUrl":"10.1097/FPC.0000000000000557","url":null,"abstract":"<p><p>This short communication serves as an update to previously published pilot study results on bronchodilator response (BDR) in children with asthma. We expanded our cohort from 54 to 165 pediatric patients seeking emergency department care for an asthma exacerbation. We obtained measured BDR before and after albuterol administration using the Pediatric Asthma Severity Score and collected genomic DNA. Based on a literature review, we analyzed whether 21 candidate single-nucleotide polymorphisms (SNPs) were associated with BDR. Among the three SNPs initially reported in our pilot study as significantly associated with BDR (rs912142, rs7081864, and rs7903366), we confirmed that rs7081864 was still significantly associated with suboptimal BDR (odds ratio, 0.47; confidence interval, 0.24-0.92). If externally validated in broader studies, simple outpatient testing for that SNP variant could help guide pharmacologic therapy for acute asthma symptoms.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":"35 3","pages":"116-118"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11871410/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524092","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":"Pharmacogenetic associations of GATA4 and KCNQ1 with ibrutinib cardiovascular toxicity.","authors":"Kelly I Nugent, Lyucheng Huang, Jai N Patel, Daniel L Hertz","doi":"10.1097/FPC.0000000000000558","DOIUrl":"10.1097/FPC.0000000000000558","url":null,"abstract":"<p><p>Ibrutinib treatment is often complicated by cardiovascular side effects (CVSEs). The objective of this retrospective pharmacogenetic study is to replicate a previously reported association of 'high-risk' patients, who are homozygous carriers of at least two of GATA4 rs804280 AA, KCNQ1 rs163182 GG, and KCNQ1 rs2237895 AA, with increased risk of hypertension or atrial fibrillation, and explore associations for other pharmacogenes (e.g. CYP3A4 , CYP3A5 , CYP2D6 , and ABCB1 ) with ibrutinib CVSEs. Univariate associations with P  < 0.05 were adjusted for significant pretreatment cardiovascular conditions. In total 57 patients were included in the analysis. In the primary analysis, 'high-risk' patients were not more likely to experience hypertension or atrial fibrillation (70 vs. 41%, chi-square P value = 0.06). In secondary analyses, 'high-risk' patients were more likely to experience any CVSE during treatment (75 vs. 41%, P  = 0.013), develop a cardiac rhythm or function disorder (65 vs. 24%, P  = 0.008), and have a treatment modification due to CVSE (45 vs. 8%, P  = 0.004). Additionally, high-risk homozygous variant genotypes of KCNQ1 rs163182 GG and rs2237895 AA were each associated with an increased likelihood of treatment modifications due to CVSE (40 vs. 11%, P  = 0.021 and 45 vs. 9%, P  = 0.004, respectively) and cardiac rhythm or function disorders (60 vs. 27%, P  = 0.037 and 60 vs. 27%, P  = 0.037). This study found supportive evidence that 'high-risk' genotype was associated with increased ibrutinib CVSEs. Validation of these associations is necessary before prospective trials testing whether personalized ibrutinib treatment approaches improve clinical outcomes.</p>","PeriodicalId":19763,"journal":{"name":"Pharmacogenetics and genomics","volume":" ","pages":"101-109"},"PeriodicalIF":1.7,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008007","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}