细胞色素P4503A4与P4503A5及多药耐药基因多态性对氨氯地平降压疗效影响研究

Effect of cytochrome P3A4,CYP3A5 and multidrug resistant gene polymorphism on antihypertensive effect of amlodipine

目的探讨细胞色素P450(CYP)3A4*1G、CYP3A5*3及多药耐药(MDR1)C1236T、MDR1 G2677T/A和MDR1 C3435T基因多态性对氨氯地平降压疗效的影响。方法纳入159名原发性高血压患者,予氨氯地平5 mg·d-1干预4周,检测相关基因型,分析不同个体CYP3A4、3A5及MDR1相关基因型分布特征,考察不同单核苷酸多态性(SNP)及MDR1单倍体对氨氯地平降压疗效的影响。结果 CYP3A4*1G*1G基因型舒张压(DBP)下降幅度显著低于CYP3A4*1G*1和CYP3A4*1*1(P<0.05);CYP3A5*3*3基因型DBP下降幅度显著高于CYP3A5*1*3和CYP3A5*1*1(P<0.05);MDR1 C1236T CC、MDR1 G2677T/A AA基因型收缩压(SBP)下降幅度显著高于其他基因型(P<0.05);MDR1 C3435T各基因型治疗前后SBP、DBP下降幅度差异均无统计学意义(P>0.05)。携带MDR1 C3435T CC、MDR1 C3435T CT基因型的患者的DBP下降幅度,女性显著高于男性(P<0.05)。对MDR1单倍体分析,各组单倍体治疗前后SBP、DBP下降幅度差异均无统计学意义(P>0.05)。结论CYP3A5*3、CYP3A4*1G基因多态性可影响氨氯地平降压疗效,MDR1各单倍体未发现与氨氯地平降压疗效相关。

Objective To analyse the association of cytochrome P450 （CYP） 3A4＊1G,CYP3A5＊3,multidrug resistant gene （MDR1） C1236T,MDR1 G2677T/A and MDR1 C3435T gene polymorphisms on antihypertensive effect of amlodipine.Methods A total of 159 patients were screened who were assigned to receive amlodipine 5 mg · d ^-1 for 4 weeks.Antihypertensive effects were analyzed according to genotype and haploid.Results Patients with CYP3A4＊1G＊1G genotype had lower diastolic blood pressure （ DBP） reduction than CYP3A4＊1G＊1 and CYP3A4＊1＊1 genotype（P〈0.05）.Patients with CYP3A5＊3＊3 gen-otype had higher DBP reduction than CYP3A5＊1＊3 and CYP3A5＊1＊1 genotype （ P 〈0.05 ）.Patients with MDR1 C1236T CC, MDR1 G2677 T/A AA genotype had higher systolic blood pressure （ SBP ） re-duction than those other genotypes （ P 〈0.05 ）.Female patients with MDR1 C3435T CC, MDR1 C3435T CT genotypes had higher DBP reduc-tion than male patients carried the same genotype（P〈0.05）.No significant relationship was found between haploid composed by MDR1（P〈0.05）.Conclusion CYP3A5＊3 and CYP3A4＊1 gene polymorphisms can affect antihypertensive effect to amlodipine.Female patients with MDR1 C3435 T CC and MDR1 C3435T CT genotypes had higher DBP reduction than male patients carried the same genotype, haploid com-posed by MDR1 was not found related to amlodipine antihypertensive effect.