{"id":"7fcc3724-6de5-5010-8e8e-1802f5727dee","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:oatp1b1-activity-lowers-statin-myopathy-risk","predicate":"reduces","statement":"The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"f08be165-b2bc-5af7-958e-149491f27deb","mechanism_event_label":"The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.","subject":{"id":"38b2f200-15ca-5db6-8d7e-2b78ee490eda","slug":"slco1b1","display_name":"Human OATP1B1 / SLCO1B1","entity_type_key":"protein"},"object":{"id":"6d822dfd-c22c-594d-9660-a539e8b22759","slug":"statin-muscle-pain","display_name":"Statin-associated muscle pain","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"f08be165-b2bc-5af7-958e-149491f27deb","stable_key":"dcb39377-0ae6-5994-8378-19d8aa9baabd:oatp1b1-activity-lowers-statin-myopathy-risk-event","event_type":"observed_relationship","label":"The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.","description":"The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"38b2f200-15ca-5db6-8d7e-2b78ee490eda","slug":"slco1b1","display_name":"Human OATP1B1 / SLCO1B1","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6d822dfd-c22c-594d-9660-a539e8b22759","slug":"statin-muscle-pain","display_name":"Statin-associated muscle pain","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ecd774bf-b45c-553f-b50b-892cf5cca148","slug":"slco1b1-c521tc-variant","display_name":"SLCO1B1 c.521T>C reduced-function variant","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"1ff526e8-51cd-5f09-a7fe-93117a7df947","slug":"atorvastatin-plasma-exposure","display_name":"Plasma atorvastatin exposure","entity_type_key":"cellular_process"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"b7de977d-fed9-5b1c-8138-fd951442b067","slug":"simvastatin","display_name":"Simvastatin","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Not applicable","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_access","value_text":"Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Review of human pharmacogenetic and pharmacokinetic studies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"SLCO1B1 c.521T>C, protein p.V174A, rs4149056","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"This is a review statement summarising several studies rather than a single measurement, the effect differs between statins, and it describes the variant's effect on activity rather than a directly measured activity-to-myopathy relationship.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Review of human pharmacogenetic and pharmacokinetic studies","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21245207/ DOI: 10.1124/pr.110.002857","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral statins","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Hepatic uptake, plasma statin concentration and skeletal muscle injury","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6992628b-1294-522b-8d8e-260234139e06","evidence_kind":"source_excerpt","locator":"Lines 68-77","start_line":68,"end_line":77,"excerpt":"## oatp1b1-activity-lowers-statin-myopathy-risk\nThe SLCO1B1 c.521T>C variant decreases OATP1B1 transporting activity, markedly increasing plasma statin concentrations, and thereby enhances the risk of statin-induced myopathy and decreases the therapeutic index of statins.\nModel/species: Review of human pharmacogenetic and pharmacokinetic studies\nTissue/system: Hepatic uptake, plasma statin concentration and skeletal muscle injury\nExposure: SLCO1B1 c.521T>C, protein p.V174A, rs4149056\nRoute: Oral statins\nDuration: Not applicable\nLimits: This is a review statement summarising several studies rather than a single measurement, the effect differs between statins, and it describes the variant's effect on activity rather than a directly measured activity-to-myopathy relationship.\nPrimary reference: Organic anion transporting polypeptide 1B1: a genetically polymorphic transporter of major importance for hepatic drug uptake. (2011). https://pubmed.ncbi.nlm.nih.gov/21245207/ DOI: 10.1124/pr.110.002857\nAccess: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.","model_system":"","directness":"reported_statement","verification_status":"source_derived_draft","notes":"","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4364bb7b-5a18-5bda-a4bc-0e2a698ab2c6","stable_key":"import-dcb39377-0ae6-5994-8378-19d8aa9baabd","title":"OATP1B1 activity and statin exposure: the step between transporter inhibition and drug concentration (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of four primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Three of the four share one research group and are recorded as one line of evidence. Study-specific citations, doses and limitations retained. Not publisher full text.","file_path":"","sha256":"0b274cf63fca0a5f8d12f53ab8bb81e04204bf547dd9dd8eacfc355a34e2bb8a","revision_id":"5544656f-04d1-56d2-9f63-ec1a8bbc4b7f","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}