{"entity": "researcher", "timestamp": "2026-11-06T19:23:29.215Z", "family": "Dagli Hernandez", "given": "Carolina", "initials": "C", "orcid": "0000-0003-2109-9399", "affiliations": ["Department of Physiology and Pharmacology, Karolinska Institutet, 17177, Stockholm, Sweden.", "Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, 05508-000, Sao Paulo, Brazil."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c6619ab558c440eb79443baf981a0ac.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c6619ab558c440eb79443baf981a0ac"}}, "publications": [{"entity": "publication", "iuid": "06bd2ed73b5f46bf96ea1498ae093e39", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/06bd2ed73b5f46bf96ea1498ae093e39.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/06bd2ed73b5f46bf96ea1498ae093e39"}}, "title": "Genetic Variant ABCC1 rs45511401 Is Associated with Increased Response to Statins in Patients with Familial Hypercholesterolemia.", "authors": [{"family": "Dagli-Hernandez", "given": "Carolina", "initials": "C", "orcid": "0000-0003-2109-9399", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c6619ab558c440eb79443baf981a0ac.json"}}, {"family": "Borges", "given": "J\u00e9ssica Bassani", "initials": "JB", "orcid": "0000-0001-8470-0132", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/973f877deb634a4fb74f3d251ddb73fc.json"}}, {"family": "Mar\u00e7al", "given": "Elisangela da Silva Rodrigues", "initials": "EDSR"}, {"family": "de Freitas", "given": "Renata Caroline Costa", "initials": "RCC"}, {"family": "Mori", "given": "Augusto Akira", "initials": "AA"}, {"family": "Gon\u00e7alves", "given": "Rodrigo Marques", "initials": "RM"}, {"family": "Faludi", "given": "Andre Arpad", "initials": "AA"}, {"family": "de Oliveira", "given": "Victor Fernandes", "initials": "VF"}, {"family": "Ferreira", "given": "Glaucio Monteiro", "initials": "GM", "orcid": "0000-0002-1952-9428", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/edd187cabd8945cfab7a8f18dca1286b.json"}}, {"family": "Bastos", "given": "Gisele Medeiros", "initials": "GM"}, {"family": "Zhou", "given": "Yitian", "initials": "Y"}, {"family": "Lauschke", "given": "Volker M", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82048d4da61547d08aa9d2bb3bae12dd.json"}}, {"family": "Cerda", "given": "Alvaro", "initials": "A", "orcid": "0000-0003-3428-8332", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/503248fb1ea14e2587549fc5a1420ac5.json"}}, {"family": "Hirata", "given": "Mario Hiroyuki", "initials": "MH", "orcid": "0000-0002-9521-7979", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7ac75c0d8474b49a5aba090c51e52fc.json"}}, {"family": "Hirata", "given": "Rosario Dominguez Crespo", "initials": "RDC", "orcid": "0000-0003-3073-5967", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6412e946f63f466cace0bfd930d374c7.json"}}], "type": "journal article", "published": "2022-04-27", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "14", "issue": "5", "issn-l": null}, "abstract": "Statins are the first-line treatment for familial hypercholesterolemia (FH), but response is highly variable due to genetic and nongenetic factors. Here, we explored the association between response and genetic variability in 114 Brazilian adult FH patients. Specifically, a panel of 84 genes was analyzed by exon-targeted gene sequencing (ETGS), and the functional impact of variants in pharmacokinetic (PK) genes was assessed using an array of functionality prediction methods. Low-density lipoprotein cholesterol (LDL-c) response to statins (reduction \u2265 50%) and statin-related adverse event (SRAE) risk were assessed in carriers of deleterious variants in PK-related genes using multivariate linear regression analyses. Fifty-eight (50.8%) FH patients responded to statins, and 24 (21.0%) had SRAE. Results of the multivariate regression analysis revealed that ABCC1 rs45511401 significantly increased LDL-c reduction after statin treatment (p < 0.05). In silico analysis of the amino-acid change using molecular docking showed that ABCC1 rs45511401 possibly impairs statin efflux. Deleterious variants in PK genes were not associated with an increased risk of SRAE. In conclusion, the deleterious variant ABCC1 rs45511401 enhanced LDL-c response in Brazilian FH patients. As such, this variant might be a promising candidate for the individualization of statin therapy.", "doi": "10.3390/pharmaceutics14050944", "pmid": "35631530", "labels": {"DDLS Fellow": null, "Yitian Zhou": null}, "xrefs": [{"db": "pmc", "key": "PMC9144204"}, {"db": "pii", "key": "pharmaceutics14050944"}], "notes": [], "created": "2026-11-06T09:29:12.145Z", "modified": "2026-11-06T09:29:12.396Z"}, {"entity": "publication", "iuid": "983d6da6473f40dc885eda005b5c305e", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/983d6da6473f40dc885eda005b5c305e.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/983d6da6473f40dc885eda005b5c305e"}}, "title": "Cardiovascular Pharmacogenomics: An Update on Clinical Studies of Antithrombotic Drugs in Brazilian Patients.", "authors": [{"family": "Hirata", "given": "Thiago Dominguez Crespo", "initials": "TDC", "orcid": "0000-0002-3967-8121", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/58db0530c2634d4d98071dc5efda5a72.json"}}, {"family": "Dagli-Hernandez", "given": "Carolina", "initials": "C", "orcid": "0000-0003-2109-9399", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c6619ab558c440eb79443baf981a0ac.json"}}, {"family": "Genvigir", "given": "Fabiana Dalla Vecchia", "initials": "FDV", "orcid": "0000-0002-7112-2879", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/eef08459787949a5a525ced75df26850.json"}}, {"family": "Lauschke", "given": "Volker Martin", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82048d4da61547d08aa9d2bb3bae12dd.json"}}, {"family": "Zhou", "given": "Yitian", "initials": "Y", "orcid": "0000-0003-3066-5444", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4e92db79d554ad283927ad7e6e54e8d.json"}}, {"family": "Hirata", "given": "Mario Hiroyuki", "initials": "MH", "orcid": "0000-0002-9521-7979", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a7ac75c0d8474b49a5aba090c51e52fc.json"}}, {"family": "Hirata", "given": "Rosario Dominguez Crespo", "initials": "RDC", "orcid": "0000-0003-3073-5967", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6412e946f63f466cace0bfd930d374c7.json"}}], "type": "journal article", "published": "2021-11-00", "journal": {"title": "Mol Diagn Ther", "issn": "1179-2000", "volume": "25", "issue": "6", "pages": "735-755", "issn-l": null}, "abstract": "Anticoagulant and antiplatelet drugs effectively prevent thrombotic events in patients with cardiovascular diseases, ischemic stroke, peripheral vascular diseases, and other thromboembolic diseases. However, genetic and non-genetic factors affect the response to antithrombotic therapy and can increase the risk of adverse events. This narrative review discusses pharmacogenomic studies on antithrombotic drugs commonly prescribed in Brazil. Multiple Brazilian studies assessed the impact of pharmacokinetic (PK) and pharmacodynamic (PD) gene variants on warfarin response. The reduced function alleles CYP2C9*2 and CYP2C9*3, and VKORC1 rs9923231 (c.-1639G>A) are associated with increased sensitivity to warfarin and a low dose requirement to prevent bleeding episodes, whereas CYP4F2 rs2108622 (p.Val433Met) carriers have higher dose requirements (warfarin resistance). These deleterious variants and non-genetic factors (age, gender, body weight, co-administered drugs, food interactions, and others) account for up to 63% of the warfarin dose variability. Few pharmacogenomics studies have explored antiplatelet drugs in Brazilian cohorts, finding associations between CYP2C19*2, PON1 rs662 and ABCC3 rs757421 genotypes and platelet responsiveness or clopidogrel PK in subjects with coronary artery disease (CAD) or acute coronary syndrome (ACS), whereas ITGB3 contributes to aspirin PK but not platelet responsiveness in diabetic patients. Brazilian guidelines on anticoagulants and antiplatelets recommend the use of a platelet aggregation test or genotyping only in selected cases of ACS subjects without ST-segment elevation taking clopidogrel, and also suggest CYP2C9 and VKORC1 genotyping before starting warfarin therapy to assess the risk of bleeding episodes or warfarin resistance.", "doi": "10.1007/s40291-021-00549-z", "pmid": "34357562", "labels": {"DDLS Fellow": null, "Yitian Zhou": null}, "xrefs": [{"db": "pii", "key": "10.1007/s40291-021-00549-z"}], "notes": [], "created": "2026-11-06T09:27:25.681Z", "modified": "2026-11-06T09:27:26.027Z"}, {"entity": "publication", "iuid": "31fbdaf4ecbc4365bfb9e950ce15844b", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/31fbdaf4ecbc4365bfb9e950ce15844b.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/31fbdaf4ecbc4365bfb9e950ce15844b"}}, "title": "Population-scale predictions of DPD and TPMT phenotypes using a quantitative pharmacogene-specific ensemble classifier.", "authors": [{"family": "Zhou", "given": "Yitian", "initials": "Y", "orcid": "0000-0003-3066-5444", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/c4e92db79d554ad283927ad7e6e54e8d.json"}}, {"family": "Dagli Hernandez", "given": "Carolina", "initials": "C", "orcid": "0000-0003-2109-9399", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/5c6619ab558c440eb79443baf981a0ac.json"}}, {"family": "Lauschke", "given": "Volker M", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/82048d4da61547d08aa9d2bb3bae12dd.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Br. J. Cancer", "issn": "1532-1827", "volume": "123", "issue": "12", "pages": "1782-1789", "issn-l": "0007-0920"}, "abstract": "Inter-individual differences in dihydropyrimidine dehydrogenase (DPYD encoding DPD) and thiopurine S-methyltransferase (TPMT) activity are important predictors for fluoropyrimidine and thiopurine toxicity. While several variants in these genes are known to decrease enzyme activities, many additional genetic variations with unclear functional consequences have been identified, complicating informed clinical decision-making in the respective carriers.\n\nWe used a novel pharmacogenetically trained ensemble classifier to analyse DPYD and TPMT genetic variability based on sequencing data from 138,842 individuals across eight populations.\n\nThe algorithm accurately predicted in vivo consequences of DPYD and TPMT variants (accuracy 91.4% compared to 95.3% in vitro). Further analysis showed high genetic complexity of DPD deficiency, advocating for sequencing-based DPYD profiling, whereas genotyping of four variants in TPMT was sufficient to explain >95% of phenotypic TPMT variability. Lastly, we provided population-scale profiles of ethnogeographic variability in DPD and TPMT phenotypes, and revealed striking interethnic differences in frequency and genetic constitution of DPD and TPMT deficiency.\n\nThese results provide the most comprehensive data set of DPYD and TPMT variability published to date with important implications for population-adjusted genetic profiling strategies of fluoropyrimidine and thiopurine risk factors and precision public health.", "doi": "10.1038/s41416-020-01084-0", "pmid": "32973300", "labels": {"DDLS Fellow": null, "Yitian Zhou": null}, "xrefs": [{"db": "pmc", "key": "PMC7722893"}, {"db": "pii", "key": "10.1038/s41416-020-01084-0"}], "notes": [], "created": "2026-11-06T09:25:20.232Z", "modified": "2026-11-06T09:25:20.378Z"}]}