SynthesisJournal of thrombosis and haemostasis : JTH2012
Influence of the paraoxonase-1 Q192R genetic variant on clopidogrel responsiveness and recurrent cardiovascular events: a systematic review and meta-analysis.
Synthesis in Journal of thrombosis and haemostasis : JTH, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 4 of them syntheses 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
23 citing papers in PubMed, 4 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- The associations of HLA-DRB1 gene polymorphisms with late-onset myasthenia gravis: a meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2020Pooled it
- Effect of UGT2B7 genotypes on plasma concentration of valproic acid: a meta-analysis.European journal of clinical pharmacology · 2018Pooled it
- Meta-analysis of effects of ABCB1 polymorphisms on clopidogrel response among patients with coronary artery disease.European journal of clinical pharmacology · 2017Pooled it
- Clinical Pharmacogenetics Implementation Consortium guidelines for CYP2C19 genotype and clopidogrel therapy: 2013 update.Clinical pharmacology and therapeutics · 2013Guideline
- Impact of selected genetic factors on clopidogrel inactive metabolite level and antiplatelet response in patients after percutaneous coronary intervention.Pharmacological reports : PR · 2021Article
- The Relevance of Noncoding DNA Variations of Paraoxonase Gene Cluster in Atherosclerosis-Related Diseases.International journal of molecular sciences · 2021Review
- Observational
- Genome-wide and candidate gene approaches of clopidogrel efficacy using pharmacodynamic and clinical end points-Rationale and design of the International Clopidogrel Pharmacogenomics Consortium (ICPC).American heart journal · 2018Review
- Paraoxonase (PON)-1: a brief overview on genetics, structure, polymorphisms and clinical relevance.Vascular health and risk management · 2018Review
- Personalizing antiplatelet prescribing using genetics for patients undergoing percutaneous coronary intervention.Expert review of cardiovascular therapy · 2017Review
- Antiplatelet treatment in essential hypertension: where do we stand?Current hypertension reports · 2015Review
- Clinical pharmacokinetics and pharmacodynamics of clopidogrel.Clinical pharmacokinetics · 2015Review
- Personalized antiplatelet and anticoagulation therapy: applications and significance of pharmacogenomics.Pharmacogenomics and personalized medicine · 2015Review
- The pharmacogenetic control of antiplatelet response: candidate genes and CYP2C19.Expert opinion on drug metabolism & toxicology · 2015Review
- Genetics of platelet inhibitor treatment.British journal of clinical pharmacology · 2014Review
- Pharmacogenetics of paraoxonase activity: elucidating the role of high-density lipoprotein in disease.Pharmacogenomics · 2013Review
- Association of PON1 genotype and haplotype with susceptibility to coronary artery disease and clinical outcomes in dual antiplatelet-treated Han Chinese patients.European journal of clinical pharmacology · 2013Article
- Pharmacogenetics and cardiovascular disease--implications for personalized medicine.Pharmacological reviews · 2013Review
- Clopidogrel variability: role of plasma protein binding alterations.British journal of clinical pharmacology · 2013Article
- Paraoxonase 1 gene polymorphism does not affect clopidogrel response variability but is associated with clinical outcome after PCI.PloS one · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundA poor biological response to clopidogrel is associated with an increased risk of major cardiovascular ischemic events (MACE). Paraoxonase 1 (PON1) enzyme activity is modulated by the PON1-Q192R variant (rs662) and was recently suggested to be strongly involved in clopidogrel bioactivation, but the influence of the PON1-Q192R variant on the risk of MACE in clopidogrel-treated patients is controversial.
objectivesTo determine whether the PON1-Q192R variant influences clopidogrel biological responsiveness and the risk of MACE in patients treated with clopidogrel.
methodsSystematic review and meta-analysis of studies of the association between the PON1-Q192R polymorphism and the biological response to clopidogrel and/or the risk of MACE during clopidogrel administration.
resultsSeventeen studies were included. In the 12 studies of the biological response to clopidogrel (n = 5302 patients), there was no significant difference between 192QQ and 192QR + 192RR subjects, whatever the laboratory method used (global mean standardized difference = 0.10 [-0.06; 0.25], P = 0.22). Eleven studies assessed the risk of MACE, four using a case-control design (n = 2739 patients) and seven a prospective design (n = 5353 patients). Overall, MACE occurred in 19% of patients in case-control studies and in 6% of patients in prospective cohort studies, with no significant difference between 192QQ and 192QR + 192RR patients (OR = 1.28 [0.97; 1.68], P = 0.08). Similar results were obtained when study design was taken into account. Heterogeneity was mainly driven by one publication.
conclusionsThis meta-analysis suggests that the PON1-Q192R polymorphism has no major impact on the risk of MACE and does not alter the biological response to clopidogrel in clopidogrel-treated patients.
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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.