Research For Correlation Factors Of On Different Curative Effect Of Amlodipine And Valsartan To Hypertension After Renal Transplantation

Objection : To approach different antihypertensive effect of amlodipine and valsartan to hypertension in renal transplantation recipients, and analyse the influence of CYP3A5 A6986G,MDR1 C3435T gene polymorphism to antihypertensive effect of amlodipine and valsartan. To estimate the fluence of gene polymorphism and acquired factors to antihypertensive effect of amlodipine and valsartan.Method : 150 patients were screened from 300 patients after renal transplantation in the third Xiang Ya hospital of central south university. acquired characteristics such as sex, age, body mass index, et al . Those patients were randomly divided into two groups: one group was administrated with Amlodipine 5mg/d, the other group was administrated with Valsartan 80mg/d. Chain reaction-restriction fragment length polymorphism (PCR-RFLP) and Polymerase chain reaction (PCR) methods were applied to detect CYP3A5 and MDR1 gene polymorphism in 150 patients, antihypertensive effect was analysed according to genotype . blood pressure, concentration of CsA, liver function and renal function were observed during 24 weeks follow-up visit.Rusult: 1. comparison of antihypertension effect between Amlodipine and Valsartan: sex, age (37.8±2.5/36.3±1.6 yr) , body weight(62.3±1.5/63.1±1.9kg), systolic blood pressure (149.5±1.9/147.3±2.7 mmHg) , diastolic pressure (86.6±0.9/86.8±1.2mmHg) and biochemical indicator, et al, show no statistical difference between amlodipine group and Valsartan group. Afte r drug intervention for 24 weeks, Target blood pressure was achieved with the initial dose of study medication (80 mg daily) in 64% of valsartan group patients and in 72% of the amlodipine group patients (5 mg daily).but no statistical difference was found in two groups (P>0.05) . the DBP reduction values was 11.2±1.0mmHg in amlodipine group and 6.9±0.6 mmHg in valsartan group, both showing significantly statistical difference (P<0.05); the SBP reduction value was 12.6±5.9mmHg and 11.9±7.5mmHg respectively, no statistical difference was found in two groups (P>0.05) . 2. Difference of antihypertensive effect in different genotype: in amlodipine group, the SBP reduction values of CYP3A5*1*1,CYP3A5*1*3 and CYP3A5*3*3 was 20.3±1.6mmHg,23.6±1.3mmHg and 21.5±1.4mmHg; DBP reduction values was 6.7±0.6 mmHg,7.0±1.9 mmHg and 11.1±0.9 mmHg, DBP reduction values of CYP3A5*1*1 is lower than CYP3A5*3*3, both showing significantly statistical difference (P<0.05). No significant relationship was found between MDR1 CC, MDR1 TC, MDR1 TT gene polymorphism and BP reducion in Amlodipine group(P>0.05). BP reducion value in patients both with CYP3A5*3*3 and MDR1 TT is higher than those both with CYP3A5*1*1 and MDR1CC genotype. No significant relationship was found between CYP3A5 and MDR1gene polymorphism with BP reducion in valsartan group(P>0.05). CYP3A5 and MDR1 genotype as the most outstanding weight factors in multifactoring regression analysis had interaction with the synergy index 6.7.3. acquired factors and CYP3A5 and MDR1 gene polymorphism used to predict antihypertensive effect in hypertension after renal tranplantation: During the treatment about hypertension of post-transplantation, amlodipine can heightened the blood concentration of CsA. multifactors such as CYP3A5 and MDR1 gene polymorphism ,age, sex, body mass index, Hepatic function and renal function ,et al,were analysed to fit logistic regression equation: P = 19.8580.346×X₂ + 0.878×X₃-7.856×X₇-8.388×X₄,χ₂=13.798, P = 0.001, the exactitude rate to predict the effect of Amlodipine is 80.6%. Another logistic regression equation was fitted: P=-0.243-9.542×X₇ + 10.317×X₃ + 1.683×X₁-1.822×X₄, the exactitude rate to predict the effect of Valsartan is 56.1%.Conclusion: 1. During the treatment about hypertension of post-transplantation, antihypertensive effect of amlodipine is better than amlodipine. Moreover, amlodipine can heightened the blood concentration of CsA.2. genetic factors were the major cause for different antihypertensive effect in hypertensive patients after renal transplantation; in patients with CYP3A5*3*3 and MDR1 TT genetype reached the highest BP reduction value,CYP3A5 and MDR1 gene polymorphism had interaction.3. in acquired factors, CYP3A5 and MDR1 gene polymorphism, age and body mass index were related with antihypertensive effect of amlodipine and valsartan.