Evidence map›Paper›PMID 38902747›Full record

ArticleBMC medical genomics2024

Molecular genomic and epigenomic characteristics related to aspirin and clopidogrel resistance.

Jei Kim, Byoung-Soo Shin, Dae-Hyun Kim, Dong-Ick Shin, Seong Hwan Ahn, Jae Guk Kim, Su Hyun Ryu, Hye Rin Moon, Hyun Goo Kang, Hyeseon Jeong and 5 more

Registry-linked trialAbstract readMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC medical genomics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03823274 (Multi-center, Prospective, Cohort Study to Evaluate the Relationship of Stroke Recurrence and Anti-platelet Resistance in Ischemic Stroke Patients), which is not on this map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

NCT03823274 completednot on this map

Multi-center, Prospective, Cohort Study to Evaluate the Relationship of Stroke Recurrence and Anti-platelet Resistance in Ischemic Stroke Patients

Typeobservational_patient_registrySponsorYuhan CorporationRan2019 to 2022Enrolled1,011ConditionsIschemic StrokeArmsAspirin, Clopidogrel
3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Promoter hypomethylation ofFrontiers in genetics · 2026
    Article
  3. Review
  4. Review
  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors.

Jei KimDepartment of Neurology, College of Medicine and Hospital, Daejeon-Chungnam Regional Cardiocerebrovascular Disease Center, Chungnam National University, Daejeon, South Korea. jeikim@cnu.ac.kr.
Byoung-Soo ShinDepartment of Neurology, Research Institute of Clinical Medicine and Biomedical Research Institute, Medical School and Hospital, Jeonbuk National University, Jeonju, South Korea.
Dae-Hyun KimDepartment of Neurology, Busan Regional Cardiocerebrovascular Disease Center, Dong-A University Hospital, Busan, South Korea.
Dong-Ick ShinDepartment of Neurology, Chungbuk Regional Cardiocerebrovascular Disease Center, Chungbuk National University Hospital, Cheongju, South Korea.
Seong Hwan AhnDepartment of Neurology, Chosun University Hospital, Gwangju, South Korea.
Jae Guk KimDepartment of Neurology, Eulji University Hospital, Daejeon, South Korea.
Su Hyun RyuDepartment of Neurology, College of Medicine and Hospital, Daejeon-Chungnam Regional Cardiocerebrovascular Disease Center, Chungnam National University, Daejeon, South Korea.
Hye Rin MoonDepartment of Neurology, College of Medicine and Hospital, Daejeon-Chungnam Regional Cardiocerebrovascular Disease Center, Chungnam National University, Daejeon, South Korea.
Hyun Goo KangDepartment of Neurology, Research Institute of Clinical Medicine and Biomedical Research Institute, Medical School and Hospital, Jeonbuk National University, Jeonju, South Korea.
Hyeseon JeongDepartment of Neurology, College of Medicine and Hospital, Daejeon-Chungnam Regional Cardiocerebrovascular Disease Center, Chungnam National University, Daejeon, South Korea.
Kyu Sun YumDepartment of Neurology, Chungbuk Regional Cardiocerebrovascular Disease Center, Chungbuk National University Hospital, Cheongju, South Korea.
Hee-Yun ChaeDepartment of Neurology, Chungbuk Regional Cardiocerebrovascular Disease Center, Chungbuk National University Hospital, Cheongju, South Korea.
Do-Hyung KimDepartment of Neurology, Eulji University Hospital, Daejeon, South Korea.
Keunsoo KangDepartment of Microbiology, College of Science & Technology, Dankook University, Cheonan, South Korea.
Jeeyeon KimDepartment of Neurology, College of Medicine and Hospital, Daejeon-Chungnam Regional Cardiocerebrovascular Disease Center, Chungnam National University, Daejeon, South Korea.

Funding

Yuhan Corporation, South Korea YMC037
6 · The paper itself

Abstract

backgroundMediators, genomic and epigenomic characteristics involving in metabolism of arachidonic acid by cyclooxygenase (COX) and lipoxygenase (ALOX) and hepatic activation of clopidogrel have been individually suggested as factors associated with resistance against aspirin and clopidogrel. The present multi-center prospective cohort study evaluated whether the mediators, genomic and epigenomic characteristics participating in arachidonic acid metabolism and clopidogrel activation could be factors that improve the prediction of the aspirin and clopidogrel resistance in addition to cardiovascular risks.

methodsWe enrolled 988 patients with transient ischemic attack and ischemic stroke who were evaluated for a recurrence of ischemic stroke to confirm clinical resistance, and measured aspirin (ARU) and P2Y12 reaction units (PRU) using VerifyNow to assess laboratory resistance 12 weeks after aspirin and clopidogrel administration. We investigated whether mediators, genotypes, and promoter methylation of genes involved in COX and ALOX metabolisms and clopidogrel activation could synergistically improve the prediction of ischemic stroke recurrence and the ARU and PRU levels by integrating to the established cardiovascular risk factors.

resultsThe logistic model to predict the recurrence used thromboxane A synthase 1 (TXAS1, rs41708) A/A genotype and ALOX12 promoter methylation as independent variables, and, improved sensitivity of recurrence prediction from 3.4% before to 13.8% after adding the mediators, genomic and epigenomic variables to the cardiovascular risks. The linear model we used to predict the ARU level included leukotriene B4, COX2 (rs20417) C/G and thromboxane A2 receptor (rs1131882) A/A genotypes with the addition of COX1 and ALOX15 promoter methylations as variables. The linear PRU prediction model included G/A and prostaglandin I receptor (rs4987262) G/A genotypes, COX2 and TXAS1 promoter methylation, as well as cytochrome P450 2C19*2 (rs4244285) A/A, G/A, and *3 (rs4986893) A/A genotypes as variables. The linear models for predicting ARU (r = 0.291, R

conclusionsThis study demonstrates that different mediators, genomic and epigenomic characteristics of arachidonic acid metabolism and clopidogrel activation synergistically improved the prediction of the aspirin and clopidogrel resistance together with the cardiovascular risk factors.

trial registrationURL: https://www. CLINICALTRIALS: gov ; Unique identifier: NCT03823274.

Indexed as

AspirinClopidogrelDrug ResistanceAgedDNA MethylationEpigenomicsFemaleGenomicsHumansMaleMiddle AgedPlatelet Aggregation InhibitorsProspective StudiesAspirinClopidogrelPlatelet Aggregation InhibitorsArachidonic acid metabolismAspirin resistanceClopidogrel activationClopidogrel resistanceEpigenomic characteristicsGenomic characteristics

Identifiers

PMID38902747
PMCPMC11188263

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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.