细胞色素P450 1A2酶基因内含子1多态性与血浆氯氮平浓度的相关研究

Relationship between polymorphism in Intron 1of cytochrome p450 1A2 gene and plasma clozapine level

目的:研究中国汉族人P450 1A2酶基因内含子1多态性以及此多态性对血浆氯氮平浓度的影响。方法:50例符合CCMD-3诊断标准的精神分裂症患者,应用药物达治疗量1周后,于晨6时取肘静脉血5毫升置于EDTA抗凝管中,分离白细胞从中抽提DNA,然后用聚合酶链反应-限制性片段长度多态性分析法(PCR-RFLP)分析患者P450 1A2酶基因内含子1多态性。测定22例应用氯氮平250 mg/d治疗患者的血浆氯氮平浓度。结果:50例精神分裂症患者中P450 1A2酶基因为A/A者22例(44%),酶基因为A/C者24例(48%),酶基因为C/C者4例(8%)。9例A/A型患者平均血浆氯氮平浓度(210.11±78.14)ng/ml,13例A/C型和C/C型患者平均血浆氯氮平浓度(228.69±82.84)ng/ml,两组间血浆氯氮平浓度无显著性差异。结论:中国汉族人P450 1A2酶基因内含子1多态性出现频率与高加索人相似,P4501A2酶基因多态性在用中等剂量氯氮平治疗精神分裂症时对血浆氯氮平浓度影响不大。

Objective：To study the Chinese polymorphism in intron 1 of cytochrome p450 1A2 gene and the relationship between the gene polymorphism and plasma clozapine level. Methods：We chose 50 schizophrenic patients which were diagnosed with the 3rd edition of Chinese classification and diagnostic criteria for mental disorders （ CCMD - 3）. One week later after using drugs to treatment quantity, at 6 we took the elbow vein blood 5ml to draw the DNA from white blood cells, then genotyped polymorphism of cytochrome p450 1A2 gene with PCR - RELP method, plasma clozapine level was determined in 22 patients which were used clozapine 250mg/D. Results ： In the 50 patients, there were 22 A/A homozygotes （44%）, 4 C/C homozygotes （ 8% ）, 24 A/C heterozygotes （48%）. The plasma clozapine level was 210.11 ± 78.14ng/ml in A/A homozygotes patients, The plasma clozapine level was 228.69 ± 82.84ng/ml in C/C homozygotes and A/C heterozygotes patients. There wasn1 significantly distinction between A/A homozygotes patients＇plasma clozapine level and C/C homozygotes A/C heterozygotes patients＇plasma clozapine level. Conclusions： Chinese polymorphism of cytochrome p450 1A2 gene in Intron 1 is similar with Caucasian. The polymorphism of cytochrome p450 1A2 gene in Intron 1 there isnt significantly influence to plasma clozapine level when clozapine is used 250mg/D.