CYP3A5基因多态性与终末期肾脏疾病患者使用钙拮抗剂降压疗效的关系  

Relationship of CYP3A5 genetic polymorphism and efficacy of calcium channel blockers in the treatment of Chinese end-stage renal disease patients

作　　者：周君[1] 陈菊[1] 

机构地区：[1]中南大学湘雅医学院附属海口医院肾内科,海口570208

出　　处：《临床肾脏病杂志》2016年第2期81-86,共6页Journal Of Clinical Nephrology

基　　金：海口市重点科技项目(NO.2013-61)

摘　　要：目的探讨终末期肾脏疾病(end-stage renal disease,ESRD)患者CYP3A5基因多态性和二氢吡啶类钙拮抗剂(calcium channel blockers,CCB)降压疗效的关系。方法选择在海口市人民医院进行规律腹膜透析或血液透析的患者215例,监测血压的同时,每3个月复查1次血红蛋白(hemoglobin,Hb)、血肌酐(SCr)、全段甲状旁腺素(immunore-active parathyroid hormone,iPTH)水平。根据血压监测结果,将患者分为血压正常组、血压达标组、严重高血压组;另外,根据所使用CCB情况,将使用CCB患者分为硝苯地平控释片组、苯磺酸氨氯地平组及非洛地平缓释片组。采用PCR-直接测序法检测CYP3A5基因多态性,同时利用Hardy-Weinberg平衡检验及多元线性回归分析CYP3A5基因与血压、CCB降压疗效间的关系。结果 CYP3A5基因频率分布符合Hardy-Weinberg平衡分布,提示来自同一孟德尔群体。CYP3A5各基因在年龄、性别、收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)、△SBP、△DBP、Hb、SCr和iPTH比较无统计学差异(P>0.05)。215例患者中血压正常组31例,高血压组184例。血压正常组中GG型14例,GA型11例,AA型6例;高血压组中GG型96例,GA型66例,AA型22例;血压正常组和高血压组各基因型比较无统计学差异(P=0.702),提示CYP3A5各基因型在血压方面无统计学差异;多元线性回归分析CYP3A5各基因型与血压的降幅无明显相关(P>0.05),提示CYP3A55基因多态性与CCB的降压疗效无明显相关。结论 CYP3A5基因多态性与ESRD患者的血压和SCr水平无显著相关,同时还发现CYP3A5基因多态性对以CCB为主要降压药物的降压疗效影响可能不大,尚需要在更大样本中进一步检验。Objective To analyze the relationship between CYP3A5 genotype and antihypertensive effect of the calcium channel blockers （CCB）. Methods We studied 215 maintenance hemodialysis or peritoneal hemodialysis patients from the Haikou Xiangya Hospital of Central South University. The levels of hemoglobin, serum creatinine and immunoreactive parathyroid hormone （iPTH） were determined every 3 months and blood pressure was measured simultaneously According to the blood pressure levels, the patients were divided into the normotensive group, the controllable hypertensive group at target blood pressure and the treatment-resistant hypertensive group. The patients were classified into the nifedipine, amlodipine and felodipine groups in terms of CCB. Multiple linear regression and the Hardy-Weinberg equilibrium test were used to analyze the relationship of CYP3A5 polymorphism and efficacy of CCB via the polymeras chain reaction and bidirectional sequencing. Results The CYP3A5 genotype distributions were in Hardy-Weinberg equilibrium providing the cue from the same Mendel group. There were no significant differences in ages, gender, SBP, DBP, ASBP, ADBP, Hb and iPTH in ESRD patients with different CYP3A5 genotypes （P〉0. 05）. There were 31 normotensive patients and 184 hypertensive patients among the 215 ESRD patients. In the normotensive group there were 14 eases of GG genotype, 14 cases of 14, 11 cases of GA genotype, and 6 cases of AA genotype. In the hypertensive group, there were 96 cases of CK; genotype, 66 cases of GA genotype, and 22 eases of AA genotype. There were no significant differences in genotypes between the normotensive patients and the hypertensive patients （P = 0. 702）, suggesting the CYP3A5 polymorphisrn was not associated with the blood pressure. Multiple linear regression showed the CYP3A5 genotype was not associated with the declined blood pressure levels （P〉0. 05）, indicating the CYP3A5 polymorphisrn was not associated with antihypertensive effect of CCB. Conclusions Our study had

关 键 词：CYP3A5 终末期肾脏疾病 钙拮抗剂 

分 类 号：R692.5[医药卫生—泌尿科学]