{"doi":"10.1021/acsptsci.3c00287","title":"Cytochrome P450 Family <i>4F2</i> and <i>4F11</i> Haplotype Mapping and Association with Hepatic Gene Expression and Vitamin K Hydroxylation Activity","abstract":"This study evaluated the underlying mechanistic links between genetic variability in vitamin K metabolic pathway genes ( CYP4F2 and CYP4F11 ) and phylloquinone hydroxylation activity using genotype- and haplotype-based approaches. Specifically, we characterized genetic variability in the CYP4F2/CYP4F11 locus and compared common single allele genotypes and common haplotypes as predictors of hepatic gene expression, enzyme abundance, and phylloquinone (VK 1 ) ω-hydroxylation kinetics. We measured CYP4F2 and CYP4F11 mRNA levels, CYP4F2 and CYP4F11 protein abundances, and the VK 1 concentration-dependent ω-hydroxylation rate in matched human liver nucleic acid and microsome samples, utilizing a novel in vitro population modeling approach. Results indicate that accounting for the CYP4F2*3 allele alone is sufficient to capture most of the genetic-derived variability in the observed phenotypes. Additionally, our findings highlight the important contribution that CYP4F11 makes toward vitamin K metabolism in the human liver.","journal":"ACS Pharmacology & Translational Science","year":2024,"id":470455,"datarank":0.16479184330021646,"base_score":1.0986122886681096,"endowment":1.0986122886681096,"self_citation_contribution":0.16479184330021646,"citation_network_contribution":0.0,"self_endowment_contribution":0.16479184330021646,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9561,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":731119,"name":"Katrina G. Claw","orcid":"0000-0003-2239-5018","position":1,"is_corresponding":false},{"id":633091,"name":"Matthew G. McDonald","orcid":"0000-0003-4667-9728","position":2,"is_corresponding":false},{"id":304535,"name":"Bhagwat Prasad","orcid":"0000-0002-9090-0912","position":3,"is_corresponding":false},{"id":252366,"name":"Allan E. Rettie","orcid":"0000-0001-9894-8753","position":4,"is_corresponding":false},{"id":331595,"name":"Kenneth E. Thummel","orcid":"0000-0002-7799-3739","position":5,"is_corresponding":false},{"id":512471,"name":"Nathan Alade","orcid":"0000-0002-1564-5659","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:05:40.740958Z","pmid":"38481683","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}