Department of Neurology, Tianjin Medical University Second Hospital, Tianjin, China.
Department of Neurology, Tianjin Medical University Second Hospital, Tianjin, China.
J Stroke Cerebrovasc Dis. 2022 Nov;31(11):106798. doi: 10.1016/j.jstrokecerebrovasdis.2022.106798. Epub 2022 Oct 7.
The relationship between CYP2C19 *2,*3 gene variants and the recurrence in ischemic stroke patients treated with clopidogrel is still controversial according to the available published literature. To evaluate correlations between CYP2C19 *2,*3 gene variants, metabolic typing according to *2, *3 SNPs (the polymorphism of rs4244285, rs4986893) and stroke recurrence, we performed this study through meta-analysis.
Literatures reporting the relationship between CYP2C19*2 and *3 polymorphism and the recurrence in ischemic stroke patients treated with clopidogrel were searched in CNKI, Wanfang Database, VIP, China Biomedical Database, PubMed and Cochrane Library from the establishment database to December 2020. Meta-analysis was performed with RevMan 5.3.
A total of 9 articles with 10 trials involving 1333 ischemic stroke patients were included. The results of meta-analysis showed CYP2C192 GA/AA genotype had a higher risk of recurrent stroke than GG in patients with ischemic stroke treated with clopidogrel(P<0.05) (GA+AA vs. GG:OR=2.50, 95% CI:1.66∼3.75;GA vs. GG:OR=2.16, 95% CI:1.41∼3.31;AA vs. GG:OR=4.40, 95% CI:2.39∼8.08; AA vs. GA:OR=2.15, 95% CI:1.20-3.84; allele A vs. G:OR=2.08, 95% CI:1.58-2.75). There was no significant difference in stroke recurrence risk between CYP2C193 GA vs. GG genotype (P=0.65)(OR=0.86,95% CI:0.44∼1.67). Compared with extensive metabolizer (EM), patients with intermediate metabolizer (IM) and poor metaholizer (PM) of CYP2C19 had a higher risk of stroke recurrent after clopidogrel treatment (IM+PM vs. EM:OR=2.20, 95%CI:1.58∼3.08, P<0.05; IM vs. EM:OR=2.06,95% CI: 1.45∼2.91, P<0.05;PM vs. EM: OR=3.32,95% CI:1.98∼5.56, P<0.05; PM vs. IM: OR=1.45,95% CI: 0.91∼2.32,P=0.11).
Among ischemic stroke patients taking clopidogrel, CYP2C192 gene mutation and CYP2C19 metabolizer were associated with stroke recurrence, CYP2C192 and 3 gene carriers were more likely to stroke recurrent than CYP2C191 gene carriers.
根据现有文献，CYP2C19*2、3 基因变异与氯吡格雷治疗的缺血性脑卒中患者的复发之间的关系仍存在争议。为了评估 CYP2C192、*3 基因变异与卒中复发之间的相关性，我们通过荟萃分析进行了此项研究。
检索中国知网、万方数据库、维普、中国生物医学文献数据库、PubMed 和 Cochrane Library 自数据库建立至 2020 年 12 月发表的关于 CYP2C192 和3 多态性与氯吡格雷治疗的缺血性脑卒中患者复发关系的文献。采用 RevMan 5.3 进行荟萃分析。
共纳入 9 篇文献，10 项试验，共纳入 1333 例缺血性脑卒中患者。荟萃分析结果显示，与 CYP2C192 GG 基因型相比，携带 GA/AA 基因型的缺血性脑卒中患者接受氯吡格雷治疗后发生卒中复发的风险更高（P<0.05）（GA+AA 与 GG：OR=2.50，95%CI：1.66～3.75；GA 与 GG：OR=2.16，95%CI：1.41～3.31；AA 与 GG：OR=4.40，95%CI：2.39～8.08；AA 与 GA：OR=2.15，95%CI：1.20～3.84；等位基因 A 与 G：OR=2.08，95%CI：1.58～2.75）。CYP2C193 GA 与 GG 基因型与卒中复发风险无显著差异（P=0.65）（OR=0.86，95%CI：0.44～1.67）。与广泛代谢型（EM）相比，CYP2C19 中间代谢型（IM）和弱代谢型（PM）患者接受氯吡格雷治疗后卒中复发风险更高（IM+PM 与 EM：OR=2.20，95%CI：1.58～3.08，P<0.05；IM 与 EM：OR=2.06，95%CI：1.45～2.91，P<0.05；PM 与 EM：OR=3.32，95%CI：1.98～5.56，P<0.05；PM 与 IM：OR=1.45，95%CI：0.91～2.32，P=0.11）。
在接受氯吡格雷治疗的缺血性脑卒中患者中，CYP2C192 基因突变和 CYP2C19 代谢物与卒中复发相关，CYP2C192 和3 基因携带者比 CYP2C191 基因携带者更易发生卒中复发。
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