Twardowschy Carlos Alexandre, Werneck Lineu César, Scola Rosana Herminia, De Paola Luciano, Silvado Carlos Eduardo
Molecular Biology Laboratory, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR, Brazil.
Arq Neuropsiquiatr. 2011 Apr;69(2A):153-8. doi: 10.1590/s0004-282x2011000200002.
CYP2C9 is a major enzyme in human drug metabolism and the polymorphism observed in the corresponding gene may affect therapeutic outcome during treatment. The distribution of variant CYP2C9 alleles and prevalence of phenytoin adverse reactions were hereby investigated in a population of patients diagnosed with epilepsy.
Allele-specific PCR analysis was carried out in order to determine frequencies of the two most common variant alleles, CYP2C92 and CYP2C93 in genomic DNA isolated from 100 epileptic patients. We also analyzed the frequency of phenytoin adverse reactions among those different genotypes groups. The data was presented as mean±standard deviation.
The mean age at enrollment was 39.6±10.3 years (range, 17-72 years) and duration of epilepsy was 26.5±11.9 years (range 3-48 years). The mean age at epilepsy onset was 13.1±12.4 years (range, 1 month-62 years). Frequencies of CYP2C91 (84%), CYP2C92 (9%) and CYP2C9*3 (7%) were similar to other published reports. Phenytoin adverse reactions were usually mild and occurred in 15% patients, without correlation with the CYP2C9 polymorphism (p=0.34).
Our findings indicate an overall similar distribution of the CYP2C9 alleles in a population of patients diagnosed with epilepsy in the South of Brazil, compared to other samples. This sample of phenytoin users showed no drug related adverse reactions and CYP2C9 allele type correlation. The role of CYP2C9 polymorphism influence on phenytoin adverse reaction remains to be determined since some literature evidence and our data found negative results.
CYP2C9是人类药物代谢中的一种主要酶，其相应基因中观察到的多态性可能会影响治疗期间的治疗效果。在此，对一组被诊断为癫痫的患者群体进行了CYP2C9变异等位基因分布及苯妥英不良反应发生率的调查。
进行等位基因特异性PCR分析，以确定从100例癫痫患者分离的基因组DNA中两种最常见变异等位基因CYP2C92和CYP2C93的频率。我们还分析了不同基因型组中苯妥英不良反应的频率。数据以平均值±标准差表示。
入组时的平均年龄为39.6±10.3岁（范围17 - 72岁），癫痫病程为26.5±11.9年（范围3 - 48年）。癫痫发作的平均年龄为13.1±12.4岁（范围1个月 - 62岁）。CYP2C91（84%）、CYP2C92（9%）和CYP2C9*3（7%）的频率与其他已发表报告相似。苯妥英不良反应通常较轻，发生在15%的患者中，与CYP2C9多态性无关（p = 0.34）。
我们的研究结果表明，与其他样本相比，在巴西南部被诊断为癫痫的患者群体中，CYP2C9等位基因的总体分布相似。该苯妥英使用者样本未显示出药物相关不良反应与CYP2C9等位基因类型之间的相关性。由于一些文献证据和我们的数据均得出阴性结果，CYP2C9多态性对苯妥英不良反应的影响作用仍有待确定。
