Effect of CYP3A5, CYP3A4, and ABCB1 Genotypes as Determinants of Tacrolimus Dose and Clinical Outcomes After Heart Transplantation

被引：26
作者：
Diaz-Molina, B. [1 ]
Tavira, B. [2 ,3 ]
Lambert, J. L. [1 ]
Bernardo, M. J. [1 ]
Alvarez, V. [2 ,3 ]
Coto, E. [2 ,3 ]
机构：
[1] Hosp Univ Cent Asturias, Dept Cardiol, Oviedo 33006, Spain
[2] Hosp Univ Cent Asturias, Mol Genet Lab, Oviedo 33006, Spain
[3] Hosp Univ Cent Asturias, Fdn Renal, Oviedo 33006, Spain
来源：
TRANSPLANTATION PROCEEDINGS | 2012年 / 44卷 / 09期
关键词：
RENAL-ALLOGRAFT RECIPIENTS; POLYMORPHISMS; IMPACT; PHARMACOKINETICS; PHARMACOGENETICS; EXPRESSION; CLEARANCE;
D O I：
10.1016/j.transproceed.2012.09.062
中图分类号：
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号：
100102 ;
摘要：
Background. Tacrolimus (Tac) is mainly metabolized by cytochrome P450 3A isoenzymes. In a cohort of heart transplant recipients, we investigated the effect of CYP3A5, CYP3A4, and ABCB1/MDR1 polymorphisms on Tac dose requirements and the risk of developing new-onset diabetes after transplantation (NODAT). Methods. A total of 65 heart transplant recipients were genotyped for 3 single nucleotide polymorphisms (SNPs) in the CYP3A5 (SNP rs776746), CYP3A4 (SNP rs2740574), and ABCB1 (SNP rs104564). The mean Tac dose values were compared between the genotypes. Results. CYP3A5*3 homozygotes (nonexpressers; n = 55, 85%) received significantly higher Tac dose compared with CYP3A5*1 carriers (expressers). No different NODAT frequencies were found between the genotypes. Conclusions. The CYP3A5 polymorphism was the main determinant of Tac dose requirements among heart transplant recipients. This common functional polymorphism had no influence on the risk of developing NODAT.
引用
收藏
页码：2635 / 2638
页数：4
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