Dataset Information

Association of GCK gene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients.

ABSTRACT: BACKGROUNDS:Clopidogrel resistance (CR), which was manifested as the failure of platelet inhibition in clopidogrel treatment, was likely to lead to cardiovascular events. Our study was aimed to explore the contribution of DNA methylation in glucokinase (GCK) to the CR risk. METHODS:Among 36 CR and 36 non-CR acute coronary syndrome (ACS) patients, the platelet functions were evaluated by VerifyNow P2Y12 assay (turbidimetric-based optical detection) and DNA methylation levels on two fragments of the CGI from the GCK were investigated through bisulfite pyrosequencing methods. In addition, the GCK mRNA expression was analyzed via quantitative real-time PCR. Lastly, the logistic regression was employed to test the interaction between GCK methylation and nongenetic variables in CR patients. RESULTS:Subunit analysis showed that in male patients without DM but suffering from dyslipidemia, the increased methylation of cg18492943 indicated a risk of poor clopidogrel response (male, NCR vs CR(%): 84.86 ± 6.29 vs 88.16 ± 4.32, P = .032; without DM, NCR vs CR (%): 84.66 ± 6.18 vs 88.16 ± 4.17, P = .029; and dyslipidemia, NCR vs CR (%): 83.81 ± 6.96 vs 88.39 ± 4.74, P = .042).In addition, GCK mRNA expression was reduced in CR patients without DM. Moreover, regression analysis indicated that the values of platelet distribution width (PDW), total cholesterol (TC), and uric acid (UA) were correlated with the incidence of CR, and hypertension lowered the CR risk. CONCLUSIONS:A higher methylation of cg18492943 in GCK gene would lower the expression of GCK mRNA, which might contribute to CR in patients without DM. Meanwhile, PDW and TC might be risk factors in CR.

SUBMITTER: Su J

PROVIDER: S-EPMC7031555 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Association of GCK gene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients.

Su Jia J Zheng Nan N Li Zhenwei Z Huangfu Ning N Mei Li L Xu Xiaolei X Zhang Li L Chen Xiaomin X

Journal of clinical laboratory analysis 20191011 2

<h4>Backgrounds</h4>Clopidogrel resistance (CR), which was manifested as the failure of platelet inhibition in clopidogrel treatment, was likely to lead to cardiovascular events. Our study was aimed to explore the contribution of DNA methylation in glucokinase (GCK) to the CR risk.<h4>Methods</h4>Among 36 CR and 36 non-CR acute coronary syndrome (ACS) patients, the platelet functions were evaluated by VerifyNow P2Y12 assay (turbidimetric-based optical detection) and DNA methylation levels on two ...[more]

PMID: 31605429

Similar Datasets

Project description:ImportanceGuidelines currently recommend ticagrelor over clopidogrel for patients with acute coronary syndrome (ACS) based on randomized clinical trial data in which ticagrelor reduced major adverse coronary events (MACE) vs clopidogrel but increased bleeding and dyspnea.ObjectiveTo compare the risk of MACE with ticagrelor vs clopidogrel in patients with ACS treated with percutaneous coronary intervention (PCI), to compare major bleeding and dyspnea, and to evaluate the association between P2Y12 inhibitor adherence and MACE.Design, setting, and participantsPopulation-based cohort study using data of patients discharged alive after PCI for ACS from the Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease registry from April 1, 2012, to March 31, 2016, with follow-up to 1 year. Analysis began April 2018.ExposuresOutpatient prescription for ticagrelor or clopidogrel within 31 days after PCI. Adherence was defined as a medication refill adherence value of 80% or higher.Main outcomes and measuresMajor adverse coronary events, a composite of all-cause death, hospitalization for ACS, unplanned coronary revascularization, or stent thrombosis within 365 days after index PCI. Secondary outcomes included hospitalization for major bleeding and emergency department visit for dyspnea.ResultsOf 11 185 individuals who underwent PCI, the median (interquartile range) age was 61 (54-71) years, and 2760 (24.7%) were women. Ticagrelor users (4076 [36.4%]) were generally younger and had fewer cardiac and noncardiac comorbidities than clopidogrel users. Ticagrelor was not associated with lower risk of MACE (adjusted hazard ratio [aHR], 0.97; 95% CI, 0.85-1.10); however, it was associated with an increased risk of major bleeding (aHR, 1.51; 95% CI, 1.29-1.78) and dyspnea (aHR, 1.98; 95% CI, 1.47-2.65). A total of 3328 ticagrelor users (81.6%) were adherent during the study vs 5256 of clopidogrel users (73.9%) (P < .001; χ2 = 86.4). In the full cohort, adherence was associated with a lower MACE risk (aHR, 0.79; 95% CI, 0.69-0.90 for adherence of ≥80% vs <80%). Differences in other secondary outcomes were not statistically significant. Sensitivity and subgroup analyses were consistent with primary analyses.Conclusions and relevanceIn this population-based cohort study of patients with ACS who underwent PCI, outpatient use of ticagrelor was not associated with a statistically significant reduction in MACE vs clopidogrel; however, it was associated with more major bleeding and dyspnea.

Project description:ImportanceCurrent guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention.ObjectiveTo determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice.Design, setting, and participantsA retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019.ExposuresTicagrelor vs clopidogrel.Main outcomes and measuresThe primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis.ResultsAfter propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group.Conclusions and relevanceAmong patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting.

Dataset Information

Association of GCK gene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients.

Publications

Association of GCK gene DNA methylation with the risk of clopidogrel resistance in acute coronary syndrome patients.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets