{"id":"e686d101-a3d7-5be5-bce5-6ca1a1f8c46c","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-pemt-hormone-induction","predicate":"impairs","statement":"The risk-associated haplotype lost hormone-inducible PEMT expression.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ee5fa44d-4b9d-523e-965e-dde39de99176","mechanism_event_label":"The expected increase in endogenous synthesis machinery was impaired.","subject":{"id":"28a059ce-9fd3-54e8-ba3f-9cc58512b565","slug":"pemt-estrogen-risk-haplotype","display_name":"PEMT estrogen-response risk haplotype in the 2011 study","entity_type_key":"gene"},"object":{"id":"c214d18f-e443-570b-987c-b94da5f94cc1","slug":"pemt-estrogen-inducibility","display_name":"Hormone-inducible PEMT expression","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"ee5fa44d-4b9d-523e-965e-dde39de99176","stable_key":"27e0c1cf-7726-5164-8b15-27a631584cd0:choline-pemt-hormone-induction-event","event_type":"biochemical_relationship","label":"The expected increase in endogenous synthesis machinery was impaired.","description":"The risk-associated haplotype lost hormone-inducible PEMT expression.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"a5acc0c5-f4ed-5b32-abfa-f9b27c025356","slug":"pemt","display_name":"Human phosphatidylethanolamine N-methyltransferase / PEMT","entity_type_key":"protein"},"role":"regulated_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"28a059ce-9fd3-54e8-ba3f-9cc58512b565","slug":"pemt-estrogen-risk-haplotype","display_name":"PEMT estrogen-response risk haplotype in the 2011 study","entity_type_key":"gene"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"c214d18f-e443-570b-987c-b94da5f94cc1","slug":"pemt-estrogen-inducibility","display_name":"Hormone-inducible PEMT expression","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/choline-research/21059658.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4\", \"start_char\": 0, \"end_char\": 1380, \"text_sha256\": \"e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Transcript-specific expression, haplotype and chromatin-binding analyses","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Estrogen stimulation across PEMT haplotypes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Choline research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"choline","display_name":"Choline","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The expected increase in endogenous synthesis machinery was impaired.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Primary hepatocytes and PEMT regulatory locus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"dd09a7fd-bb36-52b1-a093-b5c6761974a9","evidence_kind":"source_excerpt","locator":"Lines 880-891","start_line":880,"end_line":891,"excerpt":"### choline-pemt-hormone-induction\nThe risk-associated haplotype lost hormone-inducible PEMT expression.\nCondition category: machinery_impairment\nnutrient_topic: Choline research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The expected increase in endogenous synthesis machinery was impaired.\norganism: Human\ntissue_or_cell_type: Primary hepatocytes and PEMT regulatory locus\nexperimental_model: Transcript-specific expression, haplotype and chromatin-binding analyses\nlimitations: Risk is allele/haplotype-specific; not every PEMT variant or every woman has the same response.\nexposure: Estrogen stimulation across PEMT haplotypes\nevidence_span: {\"source_cache\": \"artifacts/choline-research/21059658.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4\", \"start_char\": 0, \"end_char\": 1380, \"text_sha256\": \"e2906288f8d608133ab4c746793ac5939f8c9fb157dbfd92c0af7b85064310d4\"}\n[choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922","model_system":"Transcript-specific expression, haplotype and chromatin-binding analyses","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [choline-p21059658] Aberrant estrogen regulation of PEMT results in choline deficiency-associated liver dysfunction. (2011). https://pubmed.ncbi.nlm.nih.gov/21059658/ DOI: 10.1074/jbc.m110.106922","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"0ba2f05e-5cf5-5bd7-ae5d-0ab4945fcb7b","stable_key":"import-27e0c1cf-7726-5164-8b15-27a631584cd0","title":"Choline: metabolism, signaling and nutrient connections (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"c7afe3d579eba0df6d2a4c26699c653462749e03188348f900c07748cc7282a8","revision_id":"0fa7b48f-2a3c-5adc-b13e-48727dd6f815","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}