多药耐药基因多态性与心脏移植术后环孢素肾毒性的相关性分析

目的：探讨多药耐药（ MDR1）基因多态性与心脏移植术后患者环孢素（ CsA）治疗所致肾损害的相关性。方法选取2004年1月至2012年12月在首都医科大学附属北京安贞医院行心脏移植术、术后应用含CsA的免疫抑制方案治疗并至少随访12个月的患者作为研究对象，根据CsA治疗后是否出现肾损害分为肾损害组和无肾损害组。应用患者心脏移植术后检测CsA全血浓度时留取血样提取白细胞基因组DNA。根据HapMap数据库提供的位点信息，采用基质辅助激光解析电离飞行时间质谱（ MALDI-TOF MS）技术测定MDR1基因16个标签SNP位点的基因型和等位基因频率。应用dbSNP数据库进行SNP位点等位基因频率的比对，应用非条件性二元Logistic回归分析方法分析SNP多态性与CsA所致肾损害的相关性。结果共入选65例患者。肾损害组19例，男性17例，女性2例；年龄18-59（44±13）岁。无肾损害组46例，男性39例，女性7例；年龄14-71（42±15）岁。2组患者年龄、性别分布差异均无统计学意义（均P〉0.05）。MALDI-TOF MS检测获得的2组患者16个tag SNP位点的等位基因频率与dbSNP数据库数据比较以及2组之间比较，差异均无统计学意义（均P〉0.05）。经非条件性二元Logistic回归分析，MDR1基因16个Tag SNP位点的基因型频率与肾损害组患者CsA肾毒性的发生无明显相关性。结论 MDR1基因多态性与心脏移植受者CsA治疗所致肾损害无明显相关性。

Correlation analysis on polymorphisms of multidrug resistance 1 gene and nephrotoxicity induced by cyclosporine in heart transplant recipients

Objective To explore the correlation between polymorphisms of multidrug resistance 1 （MDR1）gene and nephrotoxicity induced by cyclosporine（CsA）in heart transplant recipients. Methods The patients who received cardiac transplantation in Beijing Anzhen Hospital from January 2004 to December 2012,postoperative immunosuppression treatment with CsA,and follow-up for at least 12 months,were selected as subjects. All patients were divided into the kidney injury group and the no kidney injury group according as whether kidney injury occurred after CsA treatment. Leukocyte genomic DNA was extracted from the blood which was taken for CsA concentration monitoring after heart transplant. According to information sites in HapMap database,genotype and allele frequencies of 16 tags of MDR1 SNP were analyzed by matrix-assisted laser desorption ionization time of flight mass spectrometry（ MALDI-TOF MS）. SNP allele frequencies were compared with frequencies obtained from dbSNP database and non-conditional binary logistic regression analysis was used to analyze the correlation between the SNP genetic polymorphisms and kidney injury induced by CsA. Results A total of 65 patients were entered into this study. Of them, 19 patients were in the kidney injury group（17 males and 2 females）with age of 18-59（44 ± 13）years and 46 patients were in the no kidney injury group（39 males and 7 females）with age of 14-71（42 ± 15）years. There was no statistically significant difference in age and gender between the 2 groups（ P〉0. 05 for all comparisons）. According to MALDI-TOF MS detection results,the differences of allele frequencies in 16 tag SNP and corresponding data in dbSNP database,and the differences of allele frequencies in 16 tag SNP between the 2 groups were not statistically significant（all P〉0. 05）. Based on the non-conditional Logistic regression analysis,there was no significant correlation between genetic frequency of MDR 1 in these 16 Tag SNP and the CsA nephrotoxicity in patients with kidney injury. Conclusion No statistically significant correlation between MDR1 gene polymorphism and nephrotoxicity induced by cyclosporine in heart transplant recipients is found.