中国汉族人群中CYP3AP1基因型与CYP3A活性的相关性研究

摘要

AIM: To investigate the distribution of genotype of CYP3AP1 in Chinese Han population and the correlation with CYP3A activity. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) was employed in CYP3AP1 genotype analysis; using midazolam as probe drug, CYP3A activity of 191Chinese healthy subjects was measured by plasma l′-hydroxymidazolam/midazolam ( I′-OH-MDZ/MDZ )ratio at 1 h after oral administration of 7.5 mg midazolam. RESULTS: There was significant difference of CYP3A activity in different genotypes of CYP3AP1 in vivo (P ＜ 0.05). The activity of CYP3A in homozygous A- 44 ( CYP3AP1 * 3/CYP3AP1 * 3 ) is lower than heterozygous A-44 G (CYP3AP1 * 1/CYP3AP1 * 3 ), and the CYP3A activity in homozygous G-44 (CYP3AP1 * 1/CYP3AP1 * 1 ) is the highest.CONCLUSION: There was association between the genotype of CYP3AP1 and increased activity of CYP3Ain vivo.%目的:研究中国汉族人群中CYP3API基因型的分布特征及其与CYP3A活性的相关性.方法:以口服7.5 mg咪哒唑仑后1小时血浆中1'-羟化咪哒唑仑与咪哒唑仑的比值作为CYP3A活性的衡量指标,测定191名中国汉族健康受试者的CYP3A活性,并利用多聚酶链式反应-限制性片段长度多态性(PCR-RFLP)方法对已知CYP3A活性受试者的DNA进行CYP3AP1基因分型.结果:CYP3AP1不同基因型个体的CYP3A活性存在显著差异(P＜0.05).A-44等位基因纯合子个体的CYP3A活性低于 A-44G杂合子,而G-44等位基因纯合子个体的CYP3A活性最高.结论:CYP3AP1基因型与体内CYP3A活性的增加存在相关性.