Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol.
Differential effects of 2C9*3 and 2C9*2 variants of cytochrome P-450 CYP2C9 on sensitivity to acenocoumarol.
复制标题
细胞色素 P-450 CYP2C9 的 2C9*3 和 2C9*2 变体对醋硝香豆素敏感性的不同影响。
作者：
J. Hermida;J. Zarza;I. Alberca;R. Montes;M. López;E. Molina;Eduardo Rocha
细胞色素P-450 CYP2C9基因2C9*3和2C9*2多态性与华法林过敏和出血相关。这些基因多态对阿卡马洛尔敏感性的影响尚不清楚。对三组患者进行了研究，他们分别需要低、中、高剂量的非香豆素。年龄影响戊烯香豆素的敏感性。携带2C9*3等位基因与需要较低剂量的不动香豆素有关(优势比[OR]，6.02；95%可信区间[CI]，1.50~24.18)；80%的2C9*3等位基因携带者需要较低剂量。2C9*2等位基因与较低的非香豆素剂量需求相关(OR，2.70；95%CI，1.11-6.58)，因为需要大剂量非香豆素的风险降低(高剂量组中4.8%的患者携带2C9*2等位基因，而中剂量组和低剂量组分别为34.1%和30.2%)。因此，2C9*3的携带者可能需要较低的初始负荷量的非香豆素。由于不动香豆素对2C9*2变异体的敏感性似乎与临床无关，该药物可能成为2C9*2携带者华法林的替代药物。
The 2C9*3 and 2C9*2 polymorphisms of cytochrome P-450 CYP2C9 are associated with hypersensitivity to warfarin and bleeding. The effect of these polymorphisms on sensitivity to acenocoumarol is unknown. Three groups of patients, with low, medium, or high acenocoumarol-dose requirements, were studied. Age influenced the acenocoumarol sensitivity. Bearing the 2C9*3 allele was associated with the need for a lower acenocoumarol dose (odds ratio [OR], 6.02; 95% confidence interval [CI], 1.50-24.18); 80% of carriers of the 2C9*3 allele required a low dose. The 2C9*2 allele was associated with a lower acenocoumarol-dose requirement (OR, 2.70; 95% CI, 1.11-6.58) because of a reduced risk of the need for a high acenocoumarol dose (4.8% of the patients in the high-dose group carried the 2C9*2 allele versus 34.1% and 30.2%, respectively, in the medium-dose and low-dose groups). Therefore, carriers of 2C9*3 may need a low initial loading dose of acenocoumarol. Because acenocoumarol sensitivity with the 2C9*2 variant does not seem to be clinically relevant, the drug could be an alternative to warfarin in 2C9*2 carriers.