{"id":"09a42ccc-edfb-52cb-8fc2-d2f3223cee8c","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:slco1b1-variant-and-statin-myopathy","predicate":"increases","statement":"A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"344f77bd-5223-507a-90d1-dc47b46347cb","mechanism_event_label":"A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1.","subject":{"id":"9226abad-9f55-5a2b-974e-92cdeceba040","slug":"slco1b1-rs4363657","display_name":"SLCO1B1 rs4363657 variant","entity_type_key":"cellular_process"},"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":"344f77bd-5223-507a-90d1-dc47b46347cb","stable_key":"1fb6218a-60d1-55ea-87fe-07d15d0fc46f:slco1b1-variant-and-statin-myopathy-event","event_type":"observed_relationship","label":"A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1.","description":"A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9226abad-9f55-5a2b-974e-92cdeceba040","slug":"slco1b1-rs4363657","display_name":"SLCO1B1 rs4363657 variant","entity_type_key":"cellular_process"},"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":"38b2f200-15ca-5db6-8d7e-2b78ee490eda","slug":"slco1b1","display_name":"Human OATP1B1 / SLCO1B1","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"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":3,"notes":""}]},"contexts":[{"dimension":"duration","value_text":"Trial duration, not stated here","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":"85 subjects with definite or incipient myopathy and 90 controls, replicated in a separate trial","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Simvastatin 80 mg daily, replication at simvastatin 40 mg daily","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The statin was simvastatin, not atorvastatin, and the association is with a noncoding variant rather than a demonstrated change in transporter function in these subjects.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"85 subjects with definite or incipient myopathy and 90 controls, replicated in a separate trial","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"SLCO1B1 variants and statin-induced myopathy--a genomewide study. (2008). https://pubmed.ncbi.nlm.nih.gov/18650507/ DOI: 10.1056/NEJMoa0801936","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"route","value_text":"Oral","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue","value_text":"Hepatic statin uptake and skeletal muscle injury","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"115bfeea-d558-50e4-91d0-65e3fe5812ea","evidence_kind":"source_excerpt","locator":"Lines 133-142","start_line":133,"end_line":142,"excerpt":"## slco1b1-variant-and-statin-myopathy\nA genome-wide association study found a single strong association of statin myopathy with the rs4363657 variant within SLCO1B1, which encodes the hepatic uptake transporter OATP1B1.\nModel/species: 85 subjects with definite or incipient myopathy and 90 controls, replicated in a separate trial\nTissue/system: Hepatic statin uptake and skeletal muscle injury\nExposure: Simvastatin 80 mg daily, replication at simvastatin 40 mg daily\nRoute: Oral\nDuration: Trial duration, not stated here\nLimits: The statin was simvastatin, not atorvastatin, and the association is with a noncoding variant rather than a demonstrated change in transporter function in these subjects.\nPrimary reference: SLCO1B1 variants and statin-induced myopathy--a genomewide study. (2008). https://pubmed.ncbi.nlm.nih.gov/18650507/ DOI: 10.1056/NEJMoa0801936\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":"a4431d8c-34d7-5db7-9edf-a35f68feba39","stable_key":"import-1fb6218a-60d1-55ea-87fe-07d15d0fc46f","title":"Atorvastatin: mechanism of action from target occupancy to isoprenoids, transport, muscle and metabolism (2026-09-22)","document_type":"imported_text","citation_label":"Original AI-assisted curation of twelve primary studies resolved by PubMed title search and cross-checked against live PubMed metadata. Findings obtained with mevastatin, simvastatin or the statin class are recorded against those subjects. Study-specific citations, doses, negative findings and limitations retained. Not publisher full text.","file_path":"","sha256":"6307f1acf99f90662320328974781ee660348754257b1e1555701ad597edc8e5","revision_id":"447c5978-ba3f-58fe-ac85-664caa72e01b","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}