ArticleFrontiers in pharmacology2011
Paraoxonase (PON1 and PON3) Polymorphisms: Impact on Liver Expression and Atorvastatin-Lactone Hydrolysis.
Article in Frontiers in pharmacology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
27 citing papers in PubMed, 1 synthesis or guideline pooled it, 52 citations in OpenAlex.
- Intrinsic Factors Influencing Simvastatin and Simvastatin Acid Pharmacokinetics: Age-Related Studies in Thai Adults and Cross-Population Comparisons.Clinical and translational science · 2026Pooled it
- Physicochemical Characterization and Metabolites Identification of the Synthetic Cannabinoid MDMB-5'Br-PINACA UsingChemical research in toxicology · 2026Article
- Statins in Breast Cancer Therapy: Mechanistic Insights and Emerging Evidence.Cancer innovation · 2026Review
- The Paraoxonase (International journal of molecular sciences · 2025Review
- Regulation of Human Hydrolases and Its Implications in Pharmacokinetics and Pharmacodynamics.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- A Case-Control Study Supports Genetic Contribution of theAntioxidants (Basel, Switzerland) · 2024Article
- Effect of polymorphisms in drug metabolism and transportation on plasma concentration of atorvastatin and its metabolites in patients with chronic kidney disease.Frontiers in pharmacology · 2023Article
- The Role of Single-Nucleotide Polymorphisms in Cholangiocarcinoma: A Systematic Review.Cancers · 2022Review
- A PON for All Seasons: Comparing Paraoxonase Enzyme Substrates, Activity and Action including the Role of PON3 in Health and Disease.Antioxidants (Basel, Switzerland) · 2022Review
- Fluorine impairs carboxylesterase 1-mediated hydrolysis of T-2 toxin and increases its chondrocyte toxicity.Frontiers in nutrition · 2022Article
- Current Evidence, Challenges, and Opportunities of Physiologically Based Pharmacokinetic Models of Atorvastatin for Decision Making.Pharmaceutics · 2021Review
- The Relevance of Noncoding DNA Variations of Paraoxonase Gene Cluster in Atherosclerosis-Related Diseases.International journal of molecular sciences · 2021Review
- Antioxidant Enzymes Haplotypes and Polymorphisms Associated with Obesity in Mexican Children.Antioxidants (Basel, Switzerland) · 2020Article
- Paraoxonase 3 gene polymorphisms are associated with occupational noise-induced deafness: A matched case-control study from China.PloS one · 2020Observational
- Investigating the clinical factors and comedications associated with circulating levels of atorvastatin and its major metabolites in secondary prevention.British journal of clinical pharmacology · 2020Article
- Paraoxonase 3: Structure and Its Role in Pathophysiology of Coronary Artery Disease.Biomolecules · 2019Review
- Population Scale Retrospective Analysis Reveals Potential Risk of Cholestasis in Pregnant Women Taking Omeprazole, Lansoprazole, and Amoxicillin.Interdisciplinary sciences, computational life sciences · 2019Article
- Development, validation and application of a novel HPLC-MS/MS method for the quantification of atorvastatin, bisoprolol and clopidogrel in a large cardiovascular patient cohort.Journal of pharmaceutical and biomedical analysis · 2018Observational
- Explaining Ethnic Variability of Transporter Substrate Pharmacokinetics in Healthy Asian and Caucasian Subjects with Allele Frequencies of OATP1B1 and BCRP: A Mechanistic Modeling Analysis.Clinical pharmacokinetics · 2018Article
- Drug-Drug Interactions between Atorvastatin and Dronedarone Mediated by Monomeric CYP3A4.Biochemistry · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Atorvastatin δ-lactone, a major, pharmacologically inactive metabolite, has been associated with toxicity. In a previous study we showed that polymorphisms of UGT1A3 influence atorvastatin δ-lactone formation. Here we investigated the reverse reaction, atorvastatin δ-lactone hydrolysis, in a human liver bank. Screening of microarray data revealed paraoxonases PON1 and PON3 among 17 candidate esterases. Microsomal δ-lactone hydrolysis was significantly correlated to PON1 and PON3 protein (r(s) = 0.60; r(s) = 0.62, respectively; P < 0.0001). PON1 and PON3 were strongly correlated to each other (r(s) = 0.60) but PON1 was shown to be more extensively glycosylated than PON3. In addition a novel splice-variant of PON3 was identified. Genotyping of 40 polymorphisms within the PON-locus identified PON1 promoter polymorphisms (-108T > C, -832G > A, -1741G > A) and a tightly linked group of PON3 polymorphisms (-4984A > G, -4105G > A, -1091A > G, -746C > T, and F21F) to be associated with changes in atorvastatin δ-lactone hydrolysis and expression of PON1 but not PON3. However, carriers of the common PON1 polymorphisms L55M or Q192R showed no difference in δ-lactone hydrolysis or PON expression. Haplotype analysis revealed decreased δ-lactone hydrolysis in carriers of the most common haplotype *1 compared to carriers of haplotypes *2, *3, *4, and *7. Analysis of non-genetic factors showed association of hepatocellular and cholangiocellular carcinoma with decreased PON1 and PON3 expression, respectively. Increased C-reactive protein and γ-glutamyl transferase levels were associated with decreased protein expression of both enzymes, and increased bilirubin levels, cholestasis, and presurgical exposure to omeprazole or pantoprazole were related to decreased PON3 protein. In conclusion, PON-locus polymorphisms affect PON1 expression whereas non-genetic factors have an effect on PON1 and PON3 expression. This may influence response to therapy or adverse events in statin treatment.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.