CYP3A5、CYP3A4和ABCB1基因作为心脏移植后他克莫司剂量及临床结局决定因素的作用
Effect of CYP3A5, CYP3A4, and ABCB1 genotypes as determinants of tacrolimus dose and clinical outcomes after heart transplantation.
作者信息
Díaz-Molina B, Tavira B, Lambert J L, Bernardo M J, Alvarez V, Coto E
机构信息
Cardiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain.
出版信息
Transplant Proc. 2012 Nov;44(9):2635-8. doi: 10.1016/j.transproceed.2012.09.062.
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.
背景
他克莫司（Tac）主要通过细胞色素P450 3A同工酶代谢。在一组心脏移植受者中，我们研究了CYP3A5、CYP3A4和ABCB1/MDR1基因多态性对Tac剂量需求以及移植后新发糖尿病（NODAT）风险的影响。
方法
对65名心脏移植受者进行基因分型，检测CYP3A5（单核苷酸多态性rs776746）、CYP3A4（单核苷酸多态性rs2740574）和ABCB1（单核苷酸多态性rs104564）中的3个单核苷酸多态性。比较各基因型之间的平均Tac剂量值。
结果
与CYP3A5 1携带者（表达者）相比，CYP3A5 3纯合子（不表达者；n = 55，85%）接受的Tac剂量显著更高。各基因型之间未发现NODAT频率存在差异。
结论
CYP3A5基因多态性是心脏移植受者Tac剂量需求的主要决定因素。这种常见的功能多态性对NODAT的发生风险没有影响。
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