Ashavaid Tester F, Raje Himanshu S, Shah Bharat V, Shah Swarup A
Indian J Clin Biochem. 2011 Jan;26(1):18-21. doi: 10.1007/s12291-010-0085-z. Epub 2010 Nov 19.
Single nucleotide polymorphisms in CYP3A5 (A6986G) and MDR-1 (C3435T) genes have been shown to be associated with the pharmacokinetics of tacrolimus in case of renal transplant recipients. Knowing these genotypes of the recipients before undergoing transplantation, is therefore essential for physicians to adjust the starting dose of tacrolimus in order to avoid drug induced nephrotoxicity. We have designed an allele specific PCR method for easier and rapid detection of these polymorphisms. 20 Indian renal transplant recipients on tacrolimus who developed nephrotoxicity within 1 month of transplantation and 58 Indian non-transplant subjects having the risk factors for kidney disease i.e. hypertension or diabetes or the family history of these, have been studied for these SNPs by allele specific PCR method. The data suggest that the heterozygosity of CYP3A5 and mutant allele frequency of MDR-1 SNP is higher in transplant patients as well as in general population.
CYP3A5基因（A6986G）和MDR-1基因（C3435T）中的单核苷酸多态性已被证明与肾移植受者中他克莫司的药代动力学有关。因此，在移植前了解受者的这些基因型，对于医生调整他克莫司的起始剂量以避免药物性肾毒性至关重要。我们设计了一种等位基因特异性PCR方法，以便更轻松、快速地检测这些多态性。通过等位基因特异性PCR方法，对20名接受他克莫司治疗且在移植后1个月内发生肾毒性的印度肾移植受者，以及58名有肾病危险因素（即高血压或糖尿病或其家族病史）的印度非移植受试者进行了这些单核苷酸多态性的研究。数据表明，CYP3A5的杂合性和MDR-1单核苷酸多态性的突变等位基因频率在移植患者以及普通人群中更高。
