Tay Joshua K X, Tan Chay Hoon, Chong Siow-Ann, Tan Ene-Choo
Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Prog Neuropsychopharmacol Biol Psychiatry. 2007 Aug 15;31(6):1297-302. doi: 10.1016/j.pnpbp.2007.05.013. Epub 2007 Jun 6.
CYP1A2 is an important inducible enzyme involved in the metabolism of antipsychotics. This study examined two functional polymorphisms in the gene as potential markers in predicting prolongation of QTc interval in patients treated with antipsychotics. QT intervals were measured by 12-lead electrocardiography (ECG) for patients with a DSM-IV diagnosis of schizophrenia. Genomic DNA extracted from venous blood were genotyped for the two polymorphisms by PCR-RFLP. Statistically significant result for CYP1A2()1F was noted for all patients receiving chlorpromazine equivalent doses of above 300 mg and also for a further subgroup on antipsychotics known to be CYP1A2 substrates (p=0.007, mean QTc in ms for A/A: 395.5+/-15.1, A/C: 425.7+/-25.1, C/C: 427.3+/-20.7). For CYP1A2()1C, there was no statistically significant association between genotypes and mean QTc interval. Overall, there was a trend of those with the C allele of the CYP1A2()1F polymorphism having longer QTc intervals. The results of this study suggest that the CYP1A2()1F polymorphism may contribute to the risk of developing prolonged QT-interval in patients who are treated with higher doses of antipsychotics.
细胞色素P450 1A2（CYP1A2）是一种参与抗精神病药物代谢的重要诱导酶。本研究检测了该基因中的两个功能多态性，作为预测接受抗精神病药物治疗患者QTc间期延长的潜在标志物。采用12导联心电图（ECG）测量诊断为精神分裂症的DSM-IV患者的QT间期。从静脉血中提取基因组DNA，通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对这两个多态性进行基因分型。对于所有接受氯丙嗪等效剂量高于300mg的患者以及已知为CYP1A2底物的抗精神病药物治疗的另一亚组患者，CYP1A2（）1F具有统计学显著结果（p = 0.007，A/A基因型的平均QTc间期为395.5±15.1ms，A/C基因型为425.7±25.1ms，C/C基因型为427.3±20.7ms）。对于CYP1A2（）1C，基因型与平均QTc间期之间无统计学显著关联。总体而言，具有CYP1A2（）1F多态性C等位基因的患者有QTc间期延长的趋势。本研究结果表明，CYP1A2（）1F多态性可能增加接受高剂量抗精神病药物治疗患者发生QT间期延长的风险。
