肾移植后高血压人群中CYP3A4*1G、CYP3A5*3和MDR1 C3435T基因多态性对氨氯地平降压疗效的影响  

The Effect of CYP3A4*1G,CYP3A5*3 and MDR1 C3435T Gene Polymorphism on Antihypertensive Effect of Amlodipine in Hypertensive Patients After Renal Transplantation

作　　者：文娟[1] 黄志军[1] 袁洪[1] 邢晓为[1] 赵秋平[1] 席兰艳[1] 

机构地区：[1]中南大学湘雅三医院临床药理中心,湖南省长沙市410013

出　　处：《中国动脉硬化杂志》2011年第1期55-60,共6页Chinese Journal of Arteriosclerosis

摘　　要：目的探讨CYP3A4*1G、CYP3A5*3和MDR1 C3435T基因多态性对肾移植后高血压人群氨氯地平降压疗效的影响。方法筛选70名肾移植后高血压患者并给予氨氯地平5 mg/d干预4周,应用PCR-RFLP方法检测相关基因型,根据基因型进行分组,比较不同基因型高血压患者血压下降水平。结果 3例自动退出试验,67例患者完成试验。经氨氯地平治疗后收缩压和舒张压下降值分别为18.8±6.9 mmHg和12.7±5.4 mmHg,差异有统计学差异(P<0.05)。CYP3A5*3*3基因型舒张压下降幅度(15.0±5.0 mmHg)显著高于CYP3A5*1*3基因型(11.3±5.3 mmHg)和CYP3A5*1*1基因型(10.0±4.1 mmHg)(P<0.05),但三组间收缩压下降幅度差异无显著性(P>0.05);CYP3A4*1G*1G基因型携带者舒张压下降幅度(8.6±4.1 mmHg)显著低于CYP3A4*1G*1基因型(13.2±5.2 mmHg)和CYP3A4*1*1基因型(13.1±5.5 mmHg)(P<0.05),三组间收缩压下降幅度差异无统计学意义(P>0.05);MDR1 C3435T各基因型在治疗前后收缩压和舒张压下降幅度差异均无显著性(P>0.05);CYP3A4*1G和CYP3A5*3具有连锁性,以GGGG、AAAA、AGAG基因型最常见,其中GGGG基因型治疗前后舒张压下降幅度高于其他三组(P<0.05)。结论在肾移植后高血压治疗中,CYP3A5*3和CYP3A4*1G基因多态性可影响氨氯地平的降压疗效,CYP3A5*3*3基因型的舒张压下降幅度最大,CYP3A4*1G*1G基因型的舒张压下降幅度最小,CYP3A4*1G/CYP3A5*3组成的单倍体中GGGG基因型对舒张压下降幅度最大,MDR1C3435T未发现与氨氯地平降压疗效相关。Aim To analyse the association of CYP3A4＊1G,CYP3A5＊3 and MDR1 C3435T gene polymorphisms with the antihypertensive effect of amlodipine. Methods A total of 70 patients were screened who were diagnosed as hypertension in the first year after transplantation.The patients were assigned to receive amlodipine（5 mg/d） for 4 weeks.PCR-RFLP were applied to detect CYP3A4＊1G,CYP3A5＊3 and MDR1 C3435T gene polymorphism,and antihypertensive effects were analyzed according to genotype. Results After 4-weeks treatment,mean reductions in systolic blood pressure（SBP） and diastolic blood pressure（DBP） were 18.8±6.9 mmHg and 12.7±5.4 mmHg,respectively（P0.05）.Patients with CYP3A5＊3＊3 genotype（15.0±5.0 mmHg） had higher DBP reduction than those with CYP3A5＊1＊3（11.3±5.3 mmHg） and CYP3A5＊1＊1 genotype（10.0±4.1 mmHg）（P0.05）.No significant relationship was found between CYP3A5＊3 gene polymorphism and SBP reduction（P0.05）;Patients with CYP3 A4＊1G＊1G genotype（8.6±4.1 mmHg） had lower DBP reduction than those with CYP3A4＊1G＊1 genotype（13.2±5.2 mmHg） and CYP3A4＊1＊1 genotype（13.1±5.5 mmHg）（P0.05）.No significant relationship was found between CYP3A5＊3 gene polymorphism and SBP reduction（P0.05）;And no significant relationship was found between MDR1 C3435T and BP reduction（P0.05）.A linkage disequilibrium exists between CYP3A4＊1G and CYP3A5＊3 allele,GGGG,AAAA and AGAG were the most common combination.Patients with GGGG genotype can reach higher DBP reduction than other ones. Conclusion CYP3A5＊3 and CYP3A4＊1G gene polymorphisms can affect antihypertensive effect of amlodipine in hypertensive patients after renal transplantation,DBP reduction in patients with CYP3A5＊3＊3 genotype is higher,and DBP reduction in patients with CYP3A4＊1G＊1G genotype is lower compared with other genotypes.Patients with GGGG genotype have higher DBP reduction in all the haplotypes composed by CYP3A4＊1G and CYP3A5＊3.MDR1 3435T gene polymorphism was not fo

关 键 词：肾移植 高血压 氨氯地平 基因多态性 CYP3A4 CYP3A5 MDR1 

分 类 号：R96[医药卫生—药理学]