卡马西平所致药疹与CYP3A4*18B基因型的关联性初探

Association between CYP3A4*18B genotype and Carbamazepine-Induced Cutaneous Adverse Reactions

目的初步探讨卡马西平所致药疹与CYP3A4*18B基因型的关系,以寻找预测药疹的分子学手段。方法用PCR-RFLP法检测65例卡马西平所致药疹组患者(重型药疹患者11名,轻型药疹患者54名)、100例卡马西平耐受组患者及100例健康对照组患者的CYP3A4*18B(intron10,G20338→A)基因多态性。结果卡马西平所致药疹组CYP3A4*1/CYP3A4*1(G/G)基因型30例,CYP3A4*1/CYP3A4*18B(G/A)基因型30例,CYP3A4*18B/CYP3A4*18B(A/A)基因型5例,等位基因A频率为30.8%;卡马西平耐受组G/G基因型51例,G/A基因型42例,A/A基因型7例,等位基因A频率为28%;健康对照组G/G基因型44例,G/A基因型49例,A/A基因型7例,等位基因A频率为31.5%。各组间基因型与等位基因频率差异均无统计学意义。结论由于病例数较少,目前尚没有发现卡马西平药疹与CYP3A4*18B相关联。

Objective To explore the association between CYP3A4＊18B genotype and carbamazepineinduced cutaneous adverse reactions and find the molecular method for predicting carbamazepine-induced cutaneous adverse reactions. Methods CYP3A4＊18B（intron 10, G20338 → A） genetic polymorphisms were detected by a polymerase chain reaction restriction fragment length polymorphism（PCR-RFLP） method on 65 subjects who had carbamazepine-induced cutaneous adverse reactions, including 11 patients with Stevens-Johnson syndrome or Toxic epidermal necrolysis and 54 patients with maculopapular eruption, 100 carbamazepine-tolerant controls, and 100 normal individuals. Results In carbamazepine-induced cutaneous adverse reaction group, there were 30 subjects with CYP3A4＊1/CYP3A4＊1（G/G） genotype, 30 subjects with CYP3A4＊1/CYP3A4＊18B（G/A） genotype, and 5 subjects with CYP3A4＊18B/CYP3A4＊18B（A/A） genotype. The frequency of allele A was 30.8%. In carbamazepinetolerant controls, 51 subjects were G/G genotype, 42 subjects were G/A genotype, and 7 subjects were A/A genotype. The frequency of allele A was 28%. In normal individuals, 44 subjects were G/G genotype, 49 subjects were G/A genotype, and 7 subjects were A/A genotype. The frequency of allele A was 31.5%. The difference of neither the frequency of CYP3A4＊18B genotype nor the one of allele A between carbamazepine-induced cutaneous adverse reactions group and carbamazepine-tolerant controls had any statistical significance, and the same result was found between carbamazepine-induced cutaneous adverse reactions groups and normal controls. Conclusion The data could not show any association between carbamazepine-induced cutaneous adverse reactions and CYP3A4＊18B.