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Effect of CYP3A5 polymorphism on tacrolimus concentration during early period after kidney transplantation in recipients

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Author:
No author available
Journal Title:
CHINESE JOURNAL OF ORGAN TRANSPLANTATION
Issue:
5
DOI:
10.3760/cma.j.issn.0254-1785.2009.05.001
Key Word:
细胞色素P450CYP3A;他克莫司;血药浓度;基因;肾移植;Cytochrome P-450 CYP3A;Tacrolimus Plasma concentration;Genes;Kidney transplantation

Abstract: Objective To investigate effect of cytochrome P-450 CYP3A5 polymorphism on trough level of tacrolimus during early stage after kidney transplantation in recipients.Methods All of 90 recipients were treated with tacrolimus in combination with mycophenolate mofetil and predonisone at second or third day post-transplantation.The though levels of tacrolimus assayed by ELISA were observed for one month after transplantation,and tacrolirnus dosages were frequently adjusted to make its range from 5-10 g/L The ratio of concentration-to-dose(C/D)and decreasing rate of serum creatinine per day were recorded.PCR-RFPL method was used for analyzing occurrence of CYP3A5 polymorphisms.Results The recipients with wild homozygote(CYP3A5*1/*1),mutant homozygote (CYP3A5*3/*3),and mutant heterozygote(CYP3A5*1/*3)were 9,41 and 40 cases,respectively.The initial trough level(9.8±3.1 g/L)in patients with CYP3A5 *3/*3 was markedly higher than that in patients with CYP3A5 *1/*1,and CYP3AS *1/*3(both P<0.05).Concentration-to-dose ratio among patients with different CYP3A5 alleles was in the order of *3/*3>*1/*3> *1/*1 for the first two weeks after operation.which was markedly higher in CYP3A5 *3/*3 patients than that in patients with latter two genotypes(both P<0.05).The serum creatinine decreasing rate(127.4±CYP3A5*1/*3 patients in the first week post-transplantation(both P<0.05).Conclusion CYP3A5 genotypes can affect the trough level of tarcrolimus during the first month post-transplantation in recipients.

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