PharmGKB summary

Alvarellos, Maria L.; Sangkuhl, Katrin; Daneshjou, Roxana; Whirl‐Carrillo, Michelle; Altman, Russ B.; Klein, Teri E.

doi:10.1097/fpc.0000000000000100

Cited by 31 publications

(8 citation statements)

References 64 publications

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“…CYP4F2 plays a critical role in the metabolism of arachidonic acid, and 20-hydroxyeicosatetraeonic acid, vitamin E and vitamin K ( 44 ). A previous study ( 45 ) implicated CYP4F2 upregulation in the poor prognosis of patients with pancreatic ductal adenocarcinoma, indicating its possible value as a biomarker capable of predicting cancer progression, as well as prognosis.…”

Section: Discussionmentioning

confidence: 99%

Role of CYP4F2 as a novel biomarker regulating malignant phenotypes of liver cancer cells via the Nrf2 signaling axis

et al. 2020

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Hepatocellular carcinoma (HCC) is one of the most prevalent types of cancer worldwide. The present study attempted to identify a prognostic biomarker for HCC. RNA sequencing data from the GSE63863 dataset were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified based on a protein-protein interaction (PPI) network, and prognostic evaluation was subsequently conducted. Following lentiviral transfection, the migratory, proliferative and apoptotic abilities of cells were evaluated using wound healing, Cell Counting Kit-8, Transwell migration and apoptosis assays. A total of 192 DEGs were identified from 11 pairs of HCC and matched non-tumor samples. The PPI network revealed the top three modules, and eight genes were identified from these modules. The expression levels of cytochrome P450 family 4 subfamily F member 2 (CYP4F2) were downregulated in 50 HCC samples from The Cancer Genome Atlas and in the HCC Hep3B cell line. Low CYP4F2 expression was associated with a lower overall survival time. Functional studies revealed that CYP4F2 overexpression inhibited HCC cell proliferation and migration, and induced apoptosis. Furthermore, CYP4F2 overexpression repressed the expression of genes in the nuclear factor, erythroid 2 like 2 (Nrf2) signaling pathway, including Nrf2, heme oxygenase-1 and ferritin heavy chain 1, while increasing NAD(P)H quinone dehydrogenase 1 expression, suggesting that CYP4F2 overexpression reversed the antioxidant response of liver cancer cells. Overall, the present findings indicated that CYP4F2 may be a potential prognostic biomarker for predicting tumorigenesis and long-term survival rates in patients with HCC.

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Section: Discussionmentioning

confidence: 99%

Role of CYP4F2 as a novel biomarker regulating malignant phenotypes of liver cancer cells via the Nrf2 signaling axis

et al. 2020

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“…3 It also participates in metabolism of vitamin K and might, thus, affect synthesis of vitamin K dependent coagulation factors. 5 In healthy Chinese males, SLCO1B1 (rs113681054, rs4149056), CYP3A4*1G (rs2242480) or CYP3A5*3 (rs776746) variants did not affect ticagrelor pharmacokinetics or pharmacodynamics. 6 Another study in healthy volunteers found that CYP3A4*22 (rs35599367) carriers had elevated plasma concentrations of ticagrelor and AR-C124910XX as well as a more pronounced platelet inhibition than non-carriers, whereas the CYP3A5*3 (rs776746) allele was not associated with ticagrelor pharmacokinetics.…”

Section: Introductionmentioning

confidence: 93%

“…CYP4F2 enzyme is involved in synthesis of 20‐hydroxyeicosatetraenoic acid which may have an antiplatelet effect 3 . It also participates in metabolism of vitamin K and might, thus, affect synthesis of vitamin K dependent coagulation factors 5 . In healthy Chinese males, SLCO1B1 (rs113681054, rs4149056), CYP3A4*1G (rs2242480) or CYP3A5*3 (rs776746) variants did not affect ticagrelor pharmacokinetics or pharmacodynamics 6 .…”

Section: Introductionmentioning

confidence: 97%

CYP3A422* may increase bleeding risk in ticagrelor users

Liedes

Pajula

Vuorinen

et al. 2023

Basic Clin Pharma Tox

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“…This enzyme affects vitamins E and K metabolism. Genetic variants in CYP4F2 gene altering the bioavailability of vitamin K (e.g., c.1297G>A, p.Val433Met, rs2108622, MAF 28.5%) also have an impact on the dosing of several vitamin K antagonists, such as warfarin and acenocoumarol [40].…”

Section: Cyp4f2mentioning

confidence: 99%

Role of Genetic Variations in the Hepatic Handling of Drugs

Marin

Serrano

Monte

et al. 2020

IJMS

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The liver plays a pivotal role in drug handling due to its contribution to the processes of detoxification (phases 0 to 3). In addition, the liver is also an essential organ for the mechanism of action of many families of drugs, such as cholesterol-lowering, antidiabetic, antiviral, anticoagulant, and anticancer agents. Accordingly, the presence of genetic variants affecting a high number of genes expressed in hepatocytes has a critical clinical impact. The present review is not an exhaustive list but a general overview of the most relevant variants of genes involved in detoxification phases. The available information highlights the importance of defining the genomic profile responsible for the hepatic handling of drugs in many ways, such as (i) impaired uptake, (ii) enhanced export, (iii) altered metabolism due to decreased activation of prodrugs or enhanced inactivation of active compounds, and (iv) altered molecular targets located in the liver due to genetic changes or activation/downregulation of alternative/compensatory pathways. In conclusion, the advance in this field of modern pharmacology, which allows one to predict the outcome of the treatments and to develop more effective and selective agents able to overcome the lack of effect associated with the existence of some genetic variants, is required to step forward toward a more personalized medicine.

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PharmGKB summary

Cited by 31 publications

References 64 publications

Role of CYP4F2 as a novel biomarker regulating malignant phenotypes of liver cancer cells via the Nrf2 signaling axis

Role of CYP4F2 as a novel biomarker regulating malignant phenotypes of liver cancer cells via the Nrf2 signaling axis

CYP3A422* may increase bleeding risk in ticagrelor users

Role of Genetic Variations in the Hepatic Handling of Drugs

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PharmGKB summary

Cited by 31 publications

References 64 publications

Role of CYP4F2 as a novel biomarker regulating malignant phenotypes of liver cancer cells via the Nrf2 signaling axis

Role of CYP4F2 as a novel biomarker regulating malignant phenotypes of liver cancer cells via the Nrf2 signaling axis

CYP3A4*22 may increase bleeding risk in ticagrelor users

Role of Genetic Variations in the Hepatic Handling of Drugs

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CYP3A422* may increase bleeding risk in ticagrelor users