Alhazzani Adel A, Munisamy Murali, Karunakaran Gauthaman
Assistant Professor of Neurology, Department of Neurosciences, College of Medicine, King Khalid University, Abha, Kingdom of Saudi Arabia.
Neurosciences (Riyadh). 2017 Jan;22(1):31-37. doi: 10.17712/nsj.2017.1.20160303.
To elucidate the degree of genetic polymorphisms CYP2C19 (CYP2C192, CYP2C193) of key drug metabolizing enzymes on the antiplatelet effect of clopidogrel response in patients with acute ischemic stroke from Saudi Arabia.
A case-control study carried out at Neurology Clinics at Asser Central Hospital, Abha, Kingdom of Saudi Arabia from October 2015 to January 2016 and included 25 stroke patients responding to clopidogrel therapy and 25 stroke patients non responding to clopidogrel monotherapy. After obtaining their informed consent, the blood samples were collected and genotyped for CYP2C19 polymorphisms by the polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP Method). Allele frequencies were derived from genotypic data and platelet aggregation was measured using multiple electrode aggregometry on the multiplate analyser. Chi Square tests, p-values, odds ratio (OR) and corresponding confidence intervals were calculated for each polymorphism.
The CYP2C192 (681G>A) and CYP2C193 (636 G>A) polymorphism were seen to be in Hardy-Weinberg equilibrium and showed significant allelic and genotypic association between responders and non-responders to clopidogrel (p<0.01). The CYP2C192: allelic chi-square=21.49, p=0.000036, OR=5.52 (2.42-12.83); Genotypic Chi-square=10.27, p=0.001, OR=7.88 (1.78-9.73). The CYP2C193: Allelic chi-square=11.66, p=0.0006, OR=3.45 (1.57-7.70); genotypic chi-square=4.37, p=0.036, OR=3.69 (0.90-5.81). The variant allele (homozygous and homozygous Mutant) showed significant influence on platelet inhibition and the antiplatelet effect of clopidogrel in ischemic stroke.
Our findings provide certain evidence on the genetic effect of CYP2C19 on clopidogrel responsiveness in stroke patients from Saudi Arabia.
阐明关键药物代谢酶CYP2C19（CYP2C192、CYP2C193）的基因多态性对沙特阿拉伯急性缺血性中风患者氯吡格雷抗血小板作用反应的影响程度。
2015年10月至2016年1月在沙特阿拉伯王国阿卜哈市阿西尔中心医院神经科门诊进行了一项病例对照研究，纳入25例对氯吡格雷治疗有反应的中风患者和25例对氯吡格雷单药治疗无反应的中风患者。在获得他们的知情同意后，采集血样，并通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP法）对CYP2C19基因多态性进行基因分型。从基因型数据得出等位基因频率，并使用多电极血小板聚集仪在多板分析仪上测量血小板聚集。对每种多态性计算卡方检验、p值、比值比（OR）和相应的置信区间。
CYP2C192（681G>A）和CYP2C193（636G>A）多态性处于哈迪-温伯格平衡，并且在氯吡格雷反应者和无反应者之间显示出显著的等位基因和基因型关联（p<0.01）。CYP2C192：等位基因卡方=21.49，p=0.000036，OR=5.52（2.42-12.83）；基因型卡方=10.27，p=0.001，OR=7.88（1.78-9.73）。CYP2C193：等位基因卡方=11.66，p=0.0006，OR=3.45（1.57-7.70）；基因型卡方=4.37，p=0.036，OR=3.69（0.90-5.81）。变异等位基因（纯合子和杂合子突变体）对血小板抑制和氯吡格雷在缺血性中风中的抗血小板作用有显著影响。
我们的研究结果为CYP2C19对沙特阿拉伯中风患者氯吡格雷反应性的遗传效应提供了一定证据。
