{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:33:07Z","timestamp":1783971187413,"version":"3.55.0"},"reference-count":47,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2016\/12788-9"],"award-info":[{"award-number":["2016\/12788-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2016\/25637-0"],"award-info":[{"award-number":["2016\/25637-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2019\/19009-4"],"award-info":[{"award-number":["2019\/19009-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["Finance code 001"],"award-info":[{"award-number":["Finance code 001"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["2016\/12788-9"],"award-info":[{"award-number":["2016\/12788-9"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["2016\/25637-0"],"award-info":[{"award-number":["2016\/25637-0"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["2019\/19009-4"],"award-info":[{"award-number":["2019\/19009-4"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfeicoamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["Finance code 001"],"award-info":[{"award-number":["Finance code 001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 &lt; 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics14050944","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T22:20:20Z","timestamp":1651098020000},"page":"944","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genetic Variant ABCC1 rs45511401 Is Associated with Increased Response to Statins in Patients with Familial Hypercholesterolemia"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2109-9399","authenticated-orcid":false,"given":"Carolina","family":"Dagli-Hernandez","sequence":"first","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"},{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 171177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8470-0132","authenticated-orcid":false,"given":"J\u00e9ssica Bassani","family":"Borges","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"},{"name":"Laboratory of Molecular Research in Cardiology, Institute Dante Pazzanese of Cardiology, Sao Paulo 04012-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisangela da Silva Rodrigues","family":"Mar\u00e7al","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"},{"name":"Laboratory of Molecular Research in Cardiology, Institute Dante Pazzanese of Cardiology, Sao Paulo 04012-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renata Caroline Costa","family":"de Freitas","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto Akira","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rodrigo Marques","family":"Gon\u00e7alves","sequence":"additional","affiliation":[{"name":"Medical Clinic Division, Institute Dante Pazzanese of Cardiology, Sao Paulo 04012-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre Arpad","family":"Faludi","sequence":"additional","affiliation":[{"name":"Medical Clinic Division, Institute Dante Pazzanese of Cardiology, Sao Paulo 04012-909, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Fernandes","family":"de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1952-9428","authenticated-orcid":false,"given":"Glaucio Monteiro","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisele Medeiros","family":"Bastos","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Research in Cardiology, Institute Dante Pazzanese of Cardiology, Sao Paulo 04012-909, Brazil"},{"name":"Department of Teaching and Research, Real e Benemerita Associa\u00e7\u00e3o Portuguesa de Beneficiencia, Sao Paulo 01323-001, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitian","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 171177 Stockholm, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-6204","authenticated-orcid":false,"given":"Volker M.","family":"Lauschke","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, Karolinska Institutet, 171177 Stockholm, Sweden"},{"name":"Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Auerbachstr. 112, 70376 Stuttgart, Germany"},{"name":"University of Tuebingen, Geschwister-Scholl-Platz, 72074 T\u00fcbingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3428-8332","authenticated-orcid":false,"given":"Alvaro","family":"Cerda","sequence":"additional","affiliation":[{"name":"Center of Excellence in Translational Medicine, CEMT-BIOREN & Department of Basic Sciences, Universidad de La Frontera, Av. Alemania 0458, Temuco 4810296, Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9521-7979","authenticated-orcid":false,"given":"Mario Hiroyuki","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3073-5967","authenticated-orcid":false,"given":"Rosario Dominguez Crespo","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Clinical and Toxicological Analyses, School of Pharmaceutical Sciences, University of Sao Paulo, Sao Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1161\/ATVBAHA.108.179564","article-title":"The LDL Receptor","volume":"29","author":"Goldstein","year":"2009","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1016\/j.jacc.2020.03.057","article-title":"Worldwide Prevalence of Familial Hypercholesterolemia: Meta-Analyses of 11 Million Subjects","volume":"75","author":"Beheshti","year":"2020","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","first-page":"782","article-title":"Update of the Brazilian Guideline for Familial Hypercholesterolemia\u20142021","volume":"117","author":"Izar","year":"2021","journal-title":"Arq. Bras. Cardiol."},{"key":"ref_4","first-page":"32","article-title":"Familial Hypercholesterolemia: Review of Diagnosis, Screening, and Treatment","volume":"62","author":"Turgeon","year":"2016","journal-title":"Can. Fam. Phys."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1161\/CIRCRESAHA.118.312782","article-title":"Statin Toxicity: Mechanistic Insights and Clinical Implications","volume":"124","author":"Ward","year":"2019","journal-title":"Circ. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.atherosclerosis.2015.09.021","article-title":"Familial Hypercholesterolaemia: A Global Call to Arms","volume":"243","author":"Cole","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2526","DOI":"10.1093\/eurheartj\/ehy182","article-title":"Adverse Effects of Statin Therapy: Perception vs. the Evidence\u2014Focus on Glucose Homeostasis, Cognitive, Renal and Hepatic Function, Haemorrhagic Stroke and Cataract","volume":"39","author":"Mach","year":"2018","journal-title":"Eur. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1093\/eurheartj\/ehv043","article-title":"Statin-Associated Muscle Symptoms: Impact on Statin Therapy--European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management","volume":"36","author":"Stroes","year":"2015","journal-title":"Eur. Heart J."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.atherosclerosis.2017.08.014","article-title":"Effects of Age, Gender and Statin Dose on Lipid Levels: Results from the VOYAGER Meta-Analysis Database","volume":"265","author":"Karlson","year":"2017","journal-title":"Atherosclerosis"},{"key":"ref_10","first-page":"e002043","article-title":"Characterization of Statin Low-Density Lipoprotein Cholesterol Dose-Response Using Electronic Health Records in a Large Population-Based Cohort","volume":"11","author":"Hoffmann","year":"2018","journal-title":"Circ. Genom. Precis. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1002\/phar.1981","article-title":"Impact of Pharmacogenetics on Efficacy and Safety of Statin Therapy for Dyslipidemia","volume":"37","author":"Maxwell","year":"2017","journal-title":"Pharmacother. J. Hum. Pharmacol. Drug Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"The SEARCH Collaborative Group (2008). SLCO1B1 Variants and Statin-Induced Myopathy\u2014A Genomewide Study. N. Engl. J. Med., 359, 789\u2013799.","DOI":"10.1056\/NEJMoa0801936"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e1268","DOI":"10.1097\/MD.0000000000001268","article-title":"Association Between SLCO1B1 Gene T521C Polymorphism and Statin-Related Myopathy Risk: A Meta-Analysis of Case-Control Studies","volume":"94","author":"Hou","year":"2015","journal-title":"Medicine"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/j.jacc.2009.04.053","article-title":"The SLCO1B1*5Genetic Variant Is Associated With Statin-Induced Side Effects","volume":"54","author":"Voora","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5815","DOI":"10.3390\/ijms12095815","article-title":"Pharmacogenetics of OATP Transporters Reveals That SLCO1B1 c.388A>G Variant Is Determinant of Increased Atorvastatin Response","volume":"12","author":"Rodrigues","year":"2011","journal-title":"Int. J. Mol. Sci."},{"key":"ref_16","first-page":"76","article-title":"Late Response to Rosuvastatin and Statin-Related Myalgia Due to SLCO1B1, SLCO1B3, ABCB11, and CYP3A5 Variants in a Patient with Familial Hypercholesterolemia: A Case Report","volume":"9","author":"Faludi","year":"2020","journal-title":"Ann. Transl. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1097\/FPC.0b013e32834c6edb","article-title":"Novel CYP3A4 Intron 6 Single Nucleotide Polymorphism Is Associated with Simvastatin-Mediated Cholesterol Reduction in The Rotterdam Study","volume":"21","author":"Elens","year":"2011","journal-title":"Pharm. Genom."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cca.2008.07.032","article-title":"CYP3A5*3A Allele Is Associated with Reduced Lowering-Lipid Response to Atorvastatin in Individuals with Hypercholesterolemia","volume":"398","author":"Willrich","year":"2008","journal-title":"Clin. Chim. Acta"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1007\/s43440-021-00319-y","article-title":"Pharmacogenomics of Statins: Lipid Response and Other Outcomes in Brazilian Cohorts","volume":"74","author":"Zhou","year":"2022","journal-title":"Pharmacol. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s00228-011-1125-1","article-title":"SLCO1B1 Haplotypes Are Not Associated with Atorvastatin-Induced Myalgia in Brazilian Patients with Familial Hypercholesterolemia","volume":"68","author":"Santos","year":"2012","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1016\/j.sapharm.2020.10.007","article-title":"Genomics, Epigenomics and Pharmacogenomics of Familial Hypercholesterolemia (FHBGEP): A Study Protocol","volume":"17","author":"Borges","year":"2021","journal-title":"Res. Soc. Adm. Pharm."},{"key":"ref_22","unstructured":"World Health Organization (1998). Human Genetics Programme. Familial Hypercholesterolaemia (FH): Report of a Second WHO Consultation, WHO."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the Concentration of Low Density Lipoprotein Cholesterol in Plasma without Use of the Preparative Ultra Centrifuge","volume":"18","author":"Friedwald","year":"1972","journal-title":"Clin. Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jacl.2011.04.003","article-title":"Executive Summary Familial Hypercholesterolemia: Screening, Diagnosis and Management of Pediatric and Adult Patients Clinical Guidance from the National Lipid Association Expert Panel on Familial Hypercholesterolemia Background and Rationale","volume":"5","author":"Goldberg","year":"2011","journal-title":"J. Clin. Lipidol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1001\/jama.2015.15629","article-title":"Statins for Prevention of Cardiovascular Disease in Adults: Evidence Report and Systematic Review for the US Preventive Services Task Force","volume":"316","author":"Chou","year":"2016","journal-title":"JAMA\u2014J. Am. Med. Assoc."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1080\/14740338.2018.1394455","article-title":"Statin Drug Interactions and Related Adverse Reactions: An Update","volume":"17","author":"Bellosta","year":"2018","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.2147\/PPA.S141762","article-title":"Highly Specific Reasons for Nonadherence to Antiretroviral Therapy: Results from the German Adherence Study","volume":"11","author":"Boretzki","year":"2017","journal-title":"Patient Prefer. Adherence"},{"key":"ref_29","first-page":"115","article-title":"An Optimized Prediction Framework to Assess the Functional Impact of Pharmacogenetic Variants","volume":"19","author":"Zhou","year":"2018","journal-title":"Pharm. J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: Functional Annotation of Genetic Variants from High-Throughput Sequencing Data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jacl.2011.01.001","article-title":"The C3435T Polymorphism in ABCB1 Influences Atorvastatin Efficacy and Muscle Symptoms in a High-Risk Vascular Cohort","volume":"5","author":"Hoenig","year":"2011","journal-title":"J. Clin. Lipidol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s12944-015-0114-2","article-title":"ABCB1 C3435T Polymorphism and the Lipid-Lowering Response in Hypercholesterolemic Patients on Statins: A Meta-Analysis","volume":"14","author":"Su","year":"2015","journal-title":"Lipids Health Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.bcp.2008.09.019","article-title":"ABCB1 and ABCC1 Expression in Peripheral Mononuclear Cells Is Influenced by Gene Polymorphisms and Atorvastatin Treatment","volume":"77","author":"Rebecchi","year":"2009","journal-title":"Biochem. Pharmacol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.clpt.2005.08.003","article-title":"The Role of Common Variants of ABCB1, CYP3A4, and CYP3A5 Genes in Lipid-Lowering Efficacy and Safety of Simvastatin Treatment","volume":"78","author":"Fiegenbaum","year":"2005","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Wang, Z., Sew, P.H., Ambrose, H., Ryan, S., Chong, S.S., Lee, E.J.D., and Lee, C.G.L. (2006). Nucleotide Sequence Analyses of the MRP1 Gene in Four Populations Suggest Negative Selection on Its Coding Region. BMC Genom., 7.","DOI":"10.1186\/1471-2164-7-111"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1080\/17425255.2018.1482276","article-title":"An Update on Efflux and Uptake Transporters as Determinants of Statin Response","volume":"14","author":"Rocha","year":"2018","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1007\/s00439-020-02150-6","article-title":"Ethnogeographic and Inter-Individual Variability of Human ABC Transporters","volume":"139","author":"Xiao","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1513","DOI":"10.1093\/annonc\/mdt008","article-title":"Genetic Variability in the Multidrug Resistance Associated Protein-1 (Abcc1\/Mrp1) Predicts Hematological Toxicity in Breast Cancer Patients Receiving (Neo-)Adjuvant Chemotherapy with 5-Fluorouracil, Epirubicin and Cyclophosphamide (Fec)","volume":"24","author":"Vulsteke","year":"2013","journal-title":"Ann. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1097\/FPC.0b013e328350e270","article-title":"The G671V Variant of MRP1\/ABCC1 Links Doxorubicin-Induced Acute Cardiac Toxicity to Disposition of the Glutathione Conjugate of 4-Hydroxy-2-Trans-Nonenal","volume":"22","author":"Jungsuwadee","year":"2012","journal-title":"Pharm. Genom."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"120","DOI":"10.18869\/acadpub.ibj.21.2.120","article-title":"Association of ABCB1 (C3435T) and ABCC1 (G2012T) Polymorphisms with Clinical Response to Atorvastatin in Iranian Patients with Primary Hyperlipidemia","volume":"21","author":"Behdad","year":"2017","journal-title":"Iran. Biomed. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1111\/ahg.12231","article-title":"In Silico Characterization of Functional Single Nucleotide Polymorphisms of Folate Pathway Genes","volume":"82","author":"Vohra","year":"2018","journal-title":"Ann. Hum. Genet."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Betts, M.J., and Russell, R.B. (2003). Amino Acid Properties and Consequences of Substitutions. Bioinformatics for Geneticists, Wiley.","DOI":"10.1002\/0470867302.ch14"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1016\/j.cca.2011.11.003","article-title":"Identification of Pharmacogenetic Predictors of Lipid-Lowering Response to Atorvastatin in Chilean Subjects with Hypercholesterolemia","volume":"413","author":"Rosales","year":"2012","journal-title":"Clin. Chim. Acta"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5068","DOI":"10.1038\/ncomms6068","article-title":"Pharmacogenetic Meta-Analysis of Genome-Wide Association Studies of LDL Cholesterol Response to Statins","volume":"5","author":"Postmus","year":"2014","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1161\/CIRCGENETICS.108.818062","article-title":"Comprehensive Whole-Genome and Candidate Gene Analysis for Response to Statin Therapy in the Treating to New Targets (TNT) Cohort","volume":"2","author":"Thompson","year":"2009","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Floyd, J.S., Bloch, K.M., Brody, J.A., Maroteau, C., Siddiqui, M.K., Gregory, R., Carr, D.F., Molokhia, M., Liu, X., and Bis, J.C. (2019). Pharmacogenomics of Statin-Related Myopathy: Meta-Analysis of Rare Variants from Whole-Exome Sequencing. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0218115"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1002\/cpt.1557","article-title":"Genomewide Association Study of Statin-Induced Myopathy in Patients Recruited Using the UK Clinical Practice Research Datalink","volume":"106","author":"Carr","year":"2019","journal-title":"Clin. Pharmacol. Ther."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/5\/944\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:01:41Z","timestamp":1760137301000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/14\/5\/944"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":47,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["pharmaceutics14050944"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics14050944","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,27]]}}}