ABCB1 3435C>T基因多态性与肾移植术后环孢素肾毒性的相关性  

Correlation of ABCB1 3435C>T Polymorphism and Cyclosporine Nephrotoxicity in Chinese Renal Transplantation Recipients

作　　者：刘慧明[1,2] 辛华雯[2] 余爱荣[2] 吴笑春[2] 李罄[2] 

机构地区：[1]南方医科大学,广州510515 [2]广州军区武汉总医院临床药理科

出　　处：《中国药师》2012年第6期751-755,共5页China Pharmacist

基　　金：湖北省自然科学基金计划资助项目(编号:2009CDB010)

摘　　要：目的:观察肾移植受者ABCB1 3435C>T基因多态性对环孢素(CsA)所致慢性肾毒性的影响。方法:1995～2010年行肾移植术患者344例,根据临床指征分为慢性肾毒性组132例和对照组212例。检测所有患者ABCB1 3435C>T基因型和CsA血药浓度。χ2检验比较两组间3435C>T突变的频率分布差异,one-way ANOVA比较各基因型组间患者的CsA谷浓度和肾功能等指标的差异,logistic回归分析移植术后慢性肾毒性的危险因素。结果:在344名肾移植患者中,3435T突变等位基因发生频率为43.73%。慢性肾毒性组的TT突变基因型分布明显高于对照组(P<0.05)。ABCB1 3435C>T多态性对CsA药物动力学参数无显著影响。Logistic回归结果显示,CT和TT基因型、尸肾、男性及移植时体质量是术后慢性肾毒性发生的危险因素,移植时高龄和高BMI值是慢性肾毒性发生的保护因素。结论:ABCB1 3435C>T基因多态性对肾移植患者CsA慢性肾毒性的发生有影响。携带T基因的个体移植术后更易发生慢性肾毒性。Objective： To investigate the effects of ABCB1 3435C 〉 T polymorphism on CsA-related nephrotoxicity. Method： A total of 344 renal transplantation patients from 1995 to 2010 were enrolled. All subjects were divided into chronic nephrotoxicity group and the control group, according to the clinical occurrence. ABCB1 3435C 〉 T polymorphism was genotyped and the serum levels of CsA were measured. The .2 test was used to compare allele and genotype frequencies between the groups. One-way ANOVA test was used to compare the difference in levels of CsA and renal function indicators among the patients with different genotypes. Multivariate logistic regression tests were used to identify the risk factors in CsA-related nephrotoxicity. Result： In 344 renal transplantation pa- tients, the frequency of 3435T mutation allele was 43.73%. Compared with the control group, the distribution frequency of 3435TT genotype was significantly higher（ P 〈 0.05 ） in the chronicne phrotoxicity group. No differences in the pharmacokinetic parameters of CsA were found among the groups divided by the ABCB1 3435C 〉 T polymorphism. A logistic regression model showed that CT and TY genotypes, cadaveric kidney, male and weight were the risk factors in CsA nephrotoxicity. Conversely, older receptor age and high BMI were the protective factors in CsA nephrotoxicity. Conclusion： Genetic polymorphism of ABCB1 3435C 〉 T shows a significant effect on CsA-indueed nephrotoxicity in renal transplantationation. 3435TF genotype may be a risk factor in CsA nephrotoxicity.

关 键 词：环孢素 肾毒性 ABCB1 3435C>T 

分 类 号：R968[医药卫生—药理学]