CD80 DNA methylation and single-nucleotide polymorphism associated with clopidogrel response: a whole-genome DNA methylation analysis in acute coronary syndrome.
CD80 DNA methylation and single-nucleotide polymorphism associated with clopidogrel response: a whole-genome DNA methylation analysis in acute coronary syndrome.
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CD80 DNA 甲基化和 SNP 与氯吡格雷反应相关：急性冠状动脉综合征的全基因组 DNA 甲基化分析
DOI：
10.1016/j.rpth.2023.100093
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发表时间：
2023-02
影响因子：
4.6
通讯作者：
Chen, Xiao-Ping
中科院分区：
文献类型：
--
作者：
Song, Pei-Yuan;Li, Mu-Peng;Peng, Li-Ming;Chen, Xiao-Ping
氯吡格雷和阿司匹林双重抗血小板治疗是经皮冠状动脉介入治疗患者的主要治疗方法。然而，氯吡格雷反应的个体间差异是显著的，高治疗时血小板反应性（HTPR）可增加经皮冠状动脉介入治疗后血栓事件的风险。我们研究了可能影响氯吡格雷对DNA甲基化反应的新因素。甲基化使用850K芯片检测DNA甲基化水平。对330例急性冠脉综合征（ACS）患者在给予氯吡格雷300 mg负荷剂量或每日75 mg维持剂量至少5天后的血小板反应性指数（PRI）进行了测定。总的来说，32个发现样本显示了极端的氯吡格雷反应：16个HTPR （PRI < 75%）和16个非HTPR （PRI < 26%）。总体而言，在两组之间观察到61个差异甲基化位点（dml）。大多数位于公海和基因组的基因间区域。在验证阶段，HTPR显示CD80_cg06300880的甲基化水平较低。rs34394661 AA基因型（CD80_cg06300880位点cpg -单核苷酸多态性）携带者HTPR的几率增加（ACS患者的总优势比= 7.31,95% CI: 1.69-31.59, P = 0.008；非st段抬高型心肌梗死-ACS：优势比= 12.69,95% CI: 1.68-96.08, P = 0.01）， CD80_cg06300880甲基化降低（P < 0.0001）。多因素回归分析显示，CYP2C19代谢不良者和CD80_rs34394661 AA基因型（P = 0.009）与HTPR发病几率较高相关。相比之下，CD80_cg06300880甲基化（P = 0.002）导致非st段抬高型心肌梗死- acs患者HTPR发生率较低。CD80_cg06300880和cpg单核苷酸多态性rs34394661可能是氯吡格雷治疗后HTPR的独立预测因子。DNA甲基化改变氯吡格雷治疗时高血小板反应性（HTPR）的几率。CD80基因中的DNA甲基化位点cg06300880降低了氯吡格雷导致HTPR的几率。对于DNA序列变异rs34394661， a等位基因导致cg06300880的低甲基化。结合CYP2C19基因型和rs34394661/cg06300880可以预测氯吡格雷的HTPR。
Dual antiplatelet therapy with clopidogrel and aspirin is the primary treatment for patients who undergo percutaneous coronary intervention. However, the interindividual difference in clopidogrel response is remarkable, and high on-treatment platelet reactivity (HTPR) can increase the risk of thrombotic events after percutaneous coronary intervention. We studied novel accessible factors that possibly affect clopidogrel response in DNA methylation. Methylation 850K bead chips were used to detect DNA methylation levels. The platelet reactivity index (PRI) was determined in 330 subjects with acute coronary syndrome (ACS) after administration of clopidogrel 300 mg loading dose or at least 5 days of 75 mg daily maintenance dose. Overall, 32 discovery samples showed extreme clopidogrel response: 16 with HTPR (PRI > 75%) and 16 with non-HTPR (PRI < 26%). Overall, 61 differential methylation loci (DMLs) were observed between the 2 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 rs34394661 AA genotype, a CpG-single-nucleotide polymorphism at the CD80_cg06300880 locus, showed an increased odds for HTPR (overall odds ratio of patients with ACS = 7.31, 95% CI: 1.69-31.59, P = .008; non-ST elevation myocardial infarction-ACS: odds ratio = 12.69, 95% CI: 1.68-96.08, P = .01) and decreased CD80_cg06300880 methylation (P < .0001). Multivariate regression analysis showed that both CYP2C19 poor metabolizers and CD80_rs34394661 AA (P = .009) genotype were associated with higher odds for HTPR in the overall samples. In contrast, CD80_cg06300880 methylation (P = .002) caused lower odds for HTPR in patients with non-ST elevation myocardial infarction-ACS. CD80_cg06300880 and CpG-single-nucleotide polymorphism rs34394661 could be independent predictors of HTPR with clopidogrel therapy. DNA methylation alters odds for high on-treatment platelet reactivity (HTPR) with clopidogrel. cg06300880, a DNA methylation site in the CD80 gene, lowers the odds for HTPR with clopidogrel. For rs34394661, a variation in the DNA sequence, the A allele causes hypomethylation of cg06300880. Combing CYP2C19 genotypes and rs34394661/cg06300880 can predict HTPR with clopidogrel.
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影响因子：
46.9
作者：
Ball, Madeleine P.;Li, Jin Billy;Gao, Yuan;Lee, Je-Hyuk;LeProust, Emily M.;Park, In-Hyun;Xie, Bin;Daley, George Q.;Church, George M.
通讯作者：
Church, George M.
影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
14.9
作者：
Feng H;Conneely KN;Wu H
通讯作者：
Wu H
DOI：
10.1016/j.jcmgh.2019.04.002
发表时间：
2019-01-01
影响因子：
7.2
作者：
Fennell, Lochlan;Dumenil, Troy;Whitehall, Vicki
通讯作者：
Whitehall, Vicki
影响因子：
11.9
作者：
Evans LW;Stratton MS;Ferguson BS
通讯作者：
Ferguson BS