CD80 DNA methylation and SNP associated with clopidogrel response: a whole-genome DNA methylation analysis in acute coronary syndrome
CD80 DNA methylation and SNP associated with clopidogrel response: a whole-genome DNA methylation analysis in acute coronary syndrome
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DOI：
10.1016/j.rpth.2023.100093
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发表时间：
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影响因子：
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通讯作者：
Chen XP
中科院分区：
文献类型：
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作者：
Song PY;Li MP;Peng LM;Chen XP
Background.Dual antiplatelet therapy with clopidogrel and aspirin is the primary treatment for patients who undergo percutaneous coronary intervention (PCI). However, the interindividual difference in clopidogrel response is remarkable, and the high on-treatment platelet reactivity (HTPR) can increase the risk of thrombotic events after PCI...Objectives.We studied novel accessible factors that possibly affect the clopidogrel response in DNA methylation...Methods and Results.Methylation 850K bead chips were applied to detect DNA methylation levels. The platelet reactivity index (PRI) was determined in 330 subjects with the acute coronary syndrome (ACS) after clopidogrel 300mg loading dose (LD) or at least five days of 75 mg daily maintenance dose (MD). 32 discovery samples showed extreme clopidogrel response: 16 with HTPR (PRI>75%) and 16 with non-HTPR (PRI<26%). 61 differential methylation loci (DMLs) were observed between the two groups. Most were in the Open Sea and intergenic regions in the genome. In the validation stage, HTPR showed a lower level of CD80_cg06300880 methylation. Carriers of the rs34394661 AA genotype, a CpG-SNP at the CD80_cg06300880 locus, showed an increased odds of HTPR (overall ACS patients OR=7.31, 95% CI: 1.69-31.59, P=0.008; NSTE-ACS: OR=12.69, 95% CI:1.68-96.08, P=0.014) and decreased CD80_cg06300880 methylation (P<0.0001). Multivariate regression analysis showed that both CYP2C19 poor metabolizers and CD80_rs34394661 AA (P=0.009) genotype were associated with higher odds of HTPR in overall samples. In contrast, CD80_cg06300880 methylation (P=0.002) caused lower odds of HTPR in NSTE-ACS patients...Conclusion.CD80_cg06300880 and the CpG-SNP rs34394661 could be independent predictors of HTPR with clopidogrel therapy.
