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目的研究细胞色素CYP3A4*1G基因多态性与钙调神经蛋白抑制剂(CNI)的慢性肾毒性的相关性。方法纳入200例肾移植后一直用钙调神经蛋白抑制剂进行抗排斥并出现慢性肾毒性的中国人种患者(试验组)和200例肾移植肾移植后一直使用钙调神经蛋白抑制剂进行抗排斥且至少12个月后未出现慢性肾毒性的中国人种患者(对照组)。用聚合酶链反应—限制性内切酶片段长度多态性技术分别检测2组患者的CYP3A4*1G的突变位点基因型。基因型及等位基因患慢性肾毒性的风险率以优势比(OR)与95%可信区间(95%CI)表示。结果在试验组中,CYP3A4基因型*1/*1+*1/*1G(慢代谢)和*1G/*1G(快代谢)分别占85.5%(171/200)和14.5%(29/200);在对照组中,CYP3A4基因型*1/*1+*1/*1G和*1G/*1G分别占94.5%(189/200)和5.5%(11/200)。通过Logistic回归分析显示,CYP3A4*1G/*1G是CNI引起慢性肾毒性的危险因素(P<0.05,OR=2.914,95%CI=1.41~6.01)。结论 CYP3A4*1G/*1G可能增加肾移植术后CNI致慢性肾毒性的发生率。
Objective To investigate the relationship between cytochrome CYP3A4 * 1G gene polymorphism and chronic nephrotoxicity of calcineurin inhibitor (CNI). Methods Two hundred Chinese patients (experimental group) who had anti-rejection and chronic nephrotoxicity with calcineurin inhibitor after renal transplantation and 200 renal transplant recipients were treated with calcineurin inhibitor Chinese ethnic patients who did not develop chronic nephrotoxicity after at least 12 months of rejection (control group). The genotypes of CYP3A4 * 1G mutation sites in two groups were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Risk odds of chronic nephrotoxicity in genotypes and alleles were expressed as odds ratios (OR) with a 95% confidence interval (95% CI). Results The CYP3A4 genotypes accounted for 85.5% (171/200) and 14.5% (29/200) of the CYP3A4 genotype * 1 / * 1 + * 1 / * 1G (slow metabolism) and * 1G / * 1G ); CYP3A4 genotypes * 1 / * 1 + * 1 / * 1G and * 1G / * 1G accounted for 94.5% (189/200) and 5.5% (11/200) respectively in the control group. Logistic regression analysis showed that CYP3A4 * 1G / * 1G was a risk factor of CNI-induced chronic nephrotoxicity (P <0.05, OR = 2.914, 95% CI = 1.41-6.01). Conclusion CYP3A4 * 1G / * 1G may increase the incidence of CNI-induced chronic nephrotoxicity after renal transplantation.