ArticleAmerican journal of human genetics2008
Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: clinical significance and molecular basis.
Article in American journal of human genetics, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 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
116 citing papers in PubMed, 1 synthesis or guideline pooled it, 222 citations in OpenAlex.
- Pooled it
- Randomized evaluation of the loss-of-function carboxylesterase 1 (CES1) G143E variant on clopidogrel and ticagrelor pharmacodynamics.Clinical and translational science · 2024Trial
- Impact of carboxylesterase 1 genetic polymorphism on trandolapril activation in human liver and the pharmacokinetics and pharmacodynamics in healthy volunteers.Clinical and translational science · 2021Trial
- Ethanol Interactions With Dexmethylphenidate and dl-Methylphenidate Spheroidal Oral Drug Absorption Systems in Healthy Volunteers.Journal of clinical psychopharmacology · 2017Trial
- The impact of CES1 genotypes on the pharmacokinetics of methylphenidate in healthy Danish subjects.British journal of clinical pharmacology · 2017Trial
- CES1P1 variant -816A>C is not associated with hepatic carboxylesterase 1 expression and activity or antihypertensive effect of trandolapril.European journal of clinical pharmacology · 2016Trial
- Effect of carboxylesterase 1 c.428G > A single nucleotide variation on the pharmacokinetics of quinapril and enalapril.British journal of clinical pharmacology · 2015Trial
- Effects of alcohol on human carboxylesterase drug metabolism.Clinical pharmacokinetics · 2015Trial
- Carboxylesterase 1 is a core metabolic vulnerability of platinum-resistant high-grade serous ovarian carcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Ethanol as a Modifier of Drug Toxicity in Humans: Pathways of Toxicity and Organ-Level Consequences.International journal of molecular sciences · 2026Review
- Pharmacometabolomics Detects Unreported Clopidogrel Metabolites in the Urine of Kidney and Liver Transplant Recipients.Metabolites · 2026Article
- Sex-related differences in blood concentrations and emergence profiles following total intravenous anesthesia with remimazolam and remifentanil.Scientific reports · 2026Observational
- Triazine Thiols Decrease Apolipoprotein B Secretion From Hepatocytes Through Inhibition of Human Carboxylesterase 1.Cellular and molecular gastroenterology and hepatology · 2026Article
- Epigenetic Landscapes of Methamphetamine Addiction: Unravelling the Diagnostic Potential of Gene Methylation.Addiction biology · 2025Article
- Increased Plasma Concentrations of 6-oxo-Methylphenidate inMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2025Article
- An in vitro evaluation of common botanical extracts on carboxylesterase 1 catalytic activity.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Understanding the delivery technology used in ADHD stimulant medications can help to individualize treatment.CNS spectrums · 2025Review
- Regulation of Human Hydrolases and Its Implications in Pharmacokinetics and Pharmacodynamics.Drug metabolism and disposition: the biological fate of chemicals · 2024Review
- Discovery of a novel homocysteine thiolactone hydrolase and the catalytic activity of its natural variants.Protein science : a publication of the Protein Society · 2024Article
- Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
The human carboxylesterase 1 (CES1) gene encodes for the enzyme carboxylesterase 1, a serine esterase governing both metabolic deactivation and activation of numerous therapeutic agents. During the course of a study of the pharmacokinetics of the methyl ester racemic psychostimulant methylphenidate, profoundly elevated methylphenidate plasma concentrations, unprecedented distortions in isomer disposition, and increases in hemodynamic measures were observed in a subject of European descent. These observations led to a focused study of the subject's CES1 gene. DNA sequencing detected two coding region single-nucleotide mutations located in exons 4 and 6. The mutation in exon 4 is located in codon 143 and leads to a nonconservative substitution, p.Gly143Glu. A deletion in exon 6 at codon 260 results in a frameshift mutation, p.Asp260fs, altering residues 260-299 before truncating at a premature stop codon. The minor allele frequency of p.Gly143Glu was determined to be 3.7%, 4.3%, 2.0%, and 0% in white, black, Hispanic, and Asian populations, respectively. Of 925 individual DNA samples examined, none carried the p.Asp260fs, indicating it is an extremely rare mutation. In vitro functional studies demonstrated the catalytic functions of both p.Gly143Glu and p.Asp260fs are substantially impaired, resulting in a complete loss of hydrolytic activity toward methylphenidate. When a more sensitive esterase substrate, p-nitrophenyl acetate was utilized, only 21.4% and 0.6% catalytic efficiency (V(max)/K(m)) were determined in p.Gly143Glu and p.Asp260fs, respectively, compared to the wild-type enzyme. These findings indicate that specific CES1 gene variants can lead to clinically significant alterations in pharmacokinetics and drug response of carboxylesterase 1 substrates.
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.