Department of Nephrology, Huashan Hospital, Fudan University, Shanghai 200040, China.
Chin Med J (Engl). 2012 Dec;125(23):4233-8.
Cyclosporin A (CsA) is a substrate of both cytochrome P450 3A (CYP3A) and P-glycoprotein (P-gp), some of the single nucleotide polymorphisms (SNPs) in these genes are associated with interindividual variations in CsA pharmacokinetics. We studied the influence of these SNPs on the incidence of rejection and CsA nephrotoxicity, as well as pneumonia within one year after renal transplant and post-transplantation diabetes mellitus (PTDM), in order to find whether genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.
A total of 208 renal transplant recipients receiving CsA were genotyped for ABCB1 (C1236T, G2677T/A, and C3435T), CYP3A4 1G, and CYP3A5 3 by direct sequencing method. Retrospective case control study was utilized to identify the association between CYP3A4 1G, CYP3A5 3, ABCB1 genetic polymorphisms and CsA-related outcomes.
The patients with a CYP3A4 1G/ 1G genotype were found to have a higher incidence of acute rejection compared with those with CYP3A4 1/1.
CYP3A4 1G/1G genotype predict increased risk of acute rejection, so genetic evaluation may partly help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.
环孢素 A（CsA）是细胞色素 P450 3A（CYP3A）和 P-糖蛋白（P-gp）的底物，这些基因中的一些单核苷酸多态性（SNP）与 CsA 药代动力学的个体间差异有关。我们研究了这些 SNP 对肾移植后 1 年内排斥反应、CsA 肾毒性、肺炎以及移植后糖尿病（PTDM）的影响，以确定遗传评估是否有助于识别高危患者，并调整 CsA 治疗以优化移植物和患者的结局。
采用直接测序法对 208 例接受 CsA 治疗的肾移植受者进行 ABCB1（C1236T、G2677T/A 和 C3435T）、CYP3A4 1G 和 CYP3A5 3 的基因分型。采用回顾性病例对照研究来确定 CYP3A4 1G、CYP3A5 3 和 ABCB1 遗传多态性与 CsA 相关结局之间的关系。
与 CYP3A4 1/1 相比，CYP3A4 1G/1G 基因型的患者急性排斥反应发生率更高。
CYP3A4 1G/1G 基因型预测急性排斥反应风险增加，因此遗传评估可能部分有助于识别高危患者，并调整 CsA 治疗以优化移植物和患者的结局。
