The Effect Of Donor Kidnye MDR1Gene Polymorphism On The Nephrotoxicity And Blood Concentration Of Tacrolimus

Backgrounds and Objectives:To understand the degree of influence which the multidrug resistance gene1exon26and exon21polymorphisms of donor kidney to the acute and chronic renal toxicity and theplasma concentration of CNI drugs calls tacrolimus after renal transplantation. Exploringthe significance of kidney MDRl gene polymorphism for taking FK506in renal transplantrecipients. To guide clinicians adjust the tacrolimus dosage in the clinical to reduce the sideeffects of tacrolimus. By reasonable matching between donor and recipient, reducing thechronic toxicity of trarolimus in the long-term process of taking it, and prolonging the lifeof the transplanted kidneyMethods:Select clinical date of50patients receiving renal transplantation the first time in ourhospital from July2012to February2013period and use FK506+MMF+Pred tripleimmunosuppressive regimen after operation. Extract the blood or tissue from donor, isolatesmall amounts of DNA samples from it, and then use the samples to do PCR toamplification. Using sanger sequencing processes to detect the PRC products on3730XLsequencer to determine sample genotype. According to clinical date, compare thedifference of donor kidney MDR1exon21and exon26on patients with different genotypesthe daily dose of FK506, the plasma concentration/dose ratio(C/D) and acute/chronictoxicity to the transplant kidney.Results:1.Through gene sequencing, measuring kidney MDR1exon26genotype into CC type,CT type, TT type, exon21divided into low-expression type genotype (TT type) and highexpression of type (GG/GT/GA/AT type). The experiments were detected in50casesof genomic DNA samples, which MDR1exon21measured TT7cases, GG9cases, GT20cases, GA4cases, AT10cases; MDR1exon26measured CC18cases, TT9cases, CT23cases. The frequencies of mutant allele T and wild-type allele C in MDR1exon26were41%and59%. In MDR1exon21, the frequencies of mutant T, wild-type allele C and rare-type allele A were44%,42%and14%.2.Comparing the date of the daily dose of FK506and C/D after1week,1month,3months,6months and12months, in MDR1exon26,the CC genotype, CT type, TT typehave no significant difference (P>0.05).The same results in the low expression of typeexon21(TT type) and high expression of type (GG/GT/GA/AT-type).3.Comparing the Ccr of transplant kidney after1week,1month,3months,6months,in MDR1exon26, in MDR1exon26,the CC genotype, CT type, TT type have nosignificant difference (P>0.05).The same results in the low expression of type exon21(TTtype) and high expression of type (GG/GT/GA/AT-type). But in comparing recipients’creatinine clearance rate one year after renal transplantation, in MDR1exon26, TT-typeCcr(58.29+8.52ml/min) was significantly lower than CC-type (66.89+15.21ml/min)and CT-type (73.92+12.61ml/min)(P <0.05), the difference between CC-and CT-typehas no statistical significance. In exon21, the Ccr of low expression type (TT type)(58.29+8.52) was significantly lower than the high expression of type (GG/GT/GA/AT-type)(69.94+14.40)(P <0.05).4.Comparing the incidence of acute renal toxicity induced by FK506in one monthafter surgery, in MDR1exon21, the low expression type (TT type) is greater than theexpression of type (GG/GT/GA/AT-type)(P <0.05). There is no significant difference(P>0.05) between MDR1exon26genotypes.Conclusion:1.There is no significant correlation of FK506C/D among all gene types of MDR1exon26and exon21in donor kidney2. In the protection of graft function, reduction of acute and chronic renal toxicity ofFK506, in MDR1exon26, the CC/CT type is significantly better than TT type. And inMDR1exon21, the high-expressed type is significantly better than low-expression type.