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ABCC2 1249G>A基因多态性与肾移植患者术后吗替麦考酚酯所致不良反应的相关性研究
Association of ABCC2 1249G>A Polymorphisms with Adverse Reactions Caused by Mycophenolate Mofetil in Kidney Transplant Recipients
  
DOI:
中文关键词:  ABCC基因  吗替麦考酚酯  肾移植  药品不良反应  基因多态性
英文关键词:ABCC2  Mycophenolate mofeti  Renal transplantation  Adverse drug reaction  Gene polymorphism
基金项目:湖北省自然科学基金资助项目(编号:2009CBD010、2011CDC074)
作者单位
钟建勋 辛华雯 李维亮 熊磊 ①广州军区武汉总医院(武汉 430070)。 
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中文摘要:
      摘 要 目的:探究肾移植受者ABCC2 1249G>A基因多态性是否与吗替麦考酚酯(MMF)所致相关不良反应有关。方法:对236例患者按不良反应类型分为骨髓抑制组、胃肠道反应组、感染组和对照组,并对患者的肾源、年龄、性别、身高、质量、BMI值、透析时间、移植年月等临床资料以及患者移植术后3,6,12,24,36个月时的MMF剂量进行统计学分析;采用高效液相 荧光检测器法测定肾移植受者的霉酚酸(MPA)血药浓度;采用限制性片段长度多态性(PCR-RFLP)法检测236例患者的ABCC2 1249G>A位点多态性。结果:36例骨髓抑制,15例胃肠道反应,26例感染。ABCC2 1249G>A基因突变频率为12.08%,术后12月时GG基因型组的谷浓度显著高于GA基因型组(P<0.05),GG基因型组与GA基因型组在BMI值上的差异有统计学意义(P<0.01)。Logistic回归模型显示,用药时间、术后3月的MMF谷浓度是肾移植术后发生MMF所致骨髓抑制毒性的危险因素。结论:ABCC2 1249G>A位点的多态性与肾移植术后MMF所致相关不良反应无关。
英文摘要:
      ABSTRACT Objective: To investigate the association between the gene polymorphisms of gene ABCC2 and the adverse reactions of mycophenolate mofetil in kidney transplant patients. Methods:Dividing the 236 cases of kidney transplant patients into bone marrow suppression group, gastrointestinal tract reaction group, infection group and control group by adverse reaction type. Using HPLC fluorescence detector to determine the plasma drug concentration of MPA. Using PCR RFLP to determined single nucleotide polymorphisms genotypes of ABCC2 1249G/A, and sending PCR products sequencing directly to verify the accuracy of the agarose gel electrophoresis. Using SPSS 20.0 software to make a statistical analysis in genotype and the patients age, gender, quality, BMI, dialysis duration, cadaveric kidney or living relative kidney and the oral daily doses and concentration of MMF at 3, 6, 12, 24, 36 months. The logistic statistical analysis was used to analyze risk factors for related adverse reactions caused by MMF in post transplant patients. Results:36 cases of bone marrow suppression, 15 cases of gastrointestinal reaction, 26 cases of infection. The mutation frequency of ABCC2 1249G>A was 12.08%. The trough blood concentrations of MMF in GG group were significantly higher than GA group after 12 months postoperative (P<0.05). The values of BMI were significant difference between GG and GA group (P<0.01). A Logistic regression model showed that the medication time was the independent risk factor for the bone marrow inhibition.Conclusion:There was no significant association between the ABCC2 1249G>A genotypes and the adverse reactions caused by MMF.
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