ArticlePloS one2014
Genetic polymorphism of cytochrome P450 4F2, vitamin E level and histological response in adults and children with nonalcoholic fatty liver disease who participated in PIVENS and TONIC clinical trials.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 44 citations in OpenAlex.
- Change in plasma α-tocopherol associations with attenuated pulmonary function decline and with CYP4F2 missense variation.The American journal of clinical nutrition · 2022Trial
- Urinary α-Carboxyethyl Hydroxychromanol (α-CEHC)-A Biomarker of Vitamin E Intake: A Scoping Review.The Journal of nutrition · 2026Article
- PharmVar GeneFocus: CYP4F2.Clinical pharmacology and therapeutics · 2024Review
- CYP4F2 is a human-specific determinant of circulating N-acyl amino acid levels.The Journal of biological chemistry · 2023Article
- Genetic Factors Associated with Response to Vitamin E Treatment in NAFLD.Antioxidants (Basel, Switzerland) · 2022Review
- Marine Chitooligosaccharide Alters Intestinal Flora Structure and Regulates Hepatic Inflammatory Response to Influence Nonalcoholic Fatty Liver Disease.Marine drugs · 2022Article
- Genetic analysis of pharmacogenomic VIP variants in the Wa population from Yunnan Province of China.BMC genomic data · 2021Article
- Impact of Genetic Polymorphism on Response to Therapy in Non-Alcoholic Fatty Liver Disease.Nutrients · 2021Review
- Enjoy Carefully: The Multifaceted Role of Vitamin E in Neuro-Nutrition.International journal of molecular sciences · 2021Review
- Cardiovascular and Metabolic Protection by Vitamin E: A Matter of Treatment Strategy?Antioxidants (Basel, Switzerland) · 2020Review
- A Pilot Genome-Wide Analysis Study Identifies Loci Associated With Response to Obeticholic Acid in Patients With NASH.Hepatology communications · 2019Article
- Vitamin E Metabolic Effects and Genetic Variants: A Challenge for Precision Nutrition in Obesity and Associated Disturbances.Nutrients · 2018Review
- Genetic and Epigenetic Culprits in the Pathogenesis of Nonalcoholic Fatty Liver Disease.Journal of clinical and experimental hepatology · 2018Review
- Article
- Genetic Variations Involved in Vitamin E Status.International journal of molecular sciences · 2016Review
- Pathophysiology of Non Alcoholic Fatty Liver Disease.International journal of molecular sciences · 2016Review
- Complexity of vitamin E metabolism.World journal of biological chemistry · 2016Review
- PharmGKB summary: very important pharmacogene information for CYP4F2.Pharmacogenetics and genomics · 2015Review
- Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling.Redox biology · 2014Review
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
Abstract
Vitamin E improved liver histology in children and adults with NAFLD who participated in TONIC and PIVENS clinical trials, but with significant inter-individual variability in its efficacy. Cytochrome P450 4F2 (CYP4F2) is the major enzyme metabolizing Vit E, with two common genetic variants (V433M, rs2108622 and W12G, rs3093105) found to alter its activity. We investigated the relationship between CYP4F2 genotypes, α-tocopherol levels and histological improvement in these two trials. V433M and W12G variants were genotyped in TONIC (n = 155) and PIVENS (n = 213) DNA samples. The relationships between CYP4F2 genotypes, plasma α-tocopherol levels at baseline and weeks 48 (w48) and 96 (w96) and histological end points (overall improvement in liver histology and resolution of NASH) were investigated. As a result, the V433M genotype was significantly associated with baseline plasma α-tocopherol in the TONIC trial (p = 0.004), but not in PIVENS. Among those receiving Vit E treatment, CYP4F2 V433M genotype was associated with significantly decreased plasma α-tocopherol levels at w48 (p = 0.003 for PIVENS and p = 0.026 for TONIC) but not at w96. The w96 α-tocopherol level was significantly associated with resolution of NASH (p = 0.006) and overall histology improvement (p = 0.021)in the PIVENS, but not in the TONIC trial. There was no significant association between CYP4F2 genotypes and histological end points in either trial. Our study suggested the a moderate role of CYP4F2 polymorphisms in affecting the pharmacokinetics of Vit E as a therapeutic agent. In addition, there may be age-dependent relationship between CYP4F2 genetic variability and Vit E pharmacokinetics in NAFLD.
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