多药耐药基因多态性对钙拮抗剂治疗中国汉族终末期肾脏病患者降压疗效的影响

Relationship of MDR1 polymorphism with efficacy of calcium channel blockers in treatment of Chinese end-stage renal disease patients

摘要:

目的  探讨终末期肾脏病（ESRD）患者多药耐药基因（MDR1）多态性与二氢吡啶类钙拮抗剂（CCB）降压疗效的相关性。方法  选取215例ESRD患者，采用聚合酶链式反应-直接测序法检测MDR1基因多态性，分析MDR1基因型与CCB降压疗效的相关性。结果  MDR1基因频率符合Hardy-Weinberg平衡分布；血压达标组中CT突变杂合子型与CC野生型、TT纯合子比较，Scr增加（P <0.05）；且MDR1 C3435T基因型与CCB的降压疗效无关（P >0.05）。结论  MDR1 C3435T多态性与CCB的降压疗效无关，同时发现血压达标组中MDR1 C3435T基因多态性与Scr水平相关，是否提示CT型患者更容易进展至ESRD，尚需要在更大样本中进一步检验。

Abstract:

Objective To evaluate the association of multidrug resistance gene 1 (MDR1) polymorphism with the effectiveness of calcium channel blockers (CCB) therapy in end-stage renal disease (ESRD) patients. Methods The distribution of MDR1 polymorphism were investigated in 215 ESRD patients from Haikou Xiangya Hospital of Central South University using polymerase chain reaction and bidirectional sequencing. Multiple linear regression was used to analyze the association between polymorphisms and efficacy of CCB. Results The MDR1 genotype distribution was in Hardy-Weinberg equilibrium. The patients in the standard hypertension group who carried the CT allele had a higher serum creatinine level (P = 0.020) when compared to those who carried TT and CC genotypes (P < 0.05). There was no significant correlation between MDR1 C3435T genotypes and efficacy of CCB (P > 0.05). Conclusions MDR1 polymorphism may not associate with the effectiveness of CCB therapy in ESRD patients. The patients who carry the CT allele have a higher serum creatinine level in the standard hypertension group. Further studies are necessary to validate our findings and to examine whether patients with CT genotype have predisposition to ESRD.