Clinical interest of pharmacogenetic polymorphisms in the immunosuppressive treatment after heart transplantation.
In the transplantation field, genetic changes in a single nucleotide in the genes responsible for the transport and metabolism of an immunosuppressive drug may modify the response of the patient. The aim of this study was to evaluate the effect of single nucleotide polymorphisms (SNPs) in heart transplant recipients and their donors in association with tacrolimus and cyclosporine blood levels during the first 2 weeks after transplantation. A total of 18 blood samples from heart transplant recipients and their donors (n=36) were analyzed using Sequenom to characterize the more relevant SNPs of the ABCB1 and CYP3A5 genes for correlation with C0 (trough concentration) drug blood levels. Differences between groups were evaluated with two-way analysis of variance (ANOVA) and Bonferroni post-test. In agreement with theoretical predictions, the wild type genotype in ABCB1 SNPs (CC) tended to stabilize drug levels within the therapeutic range, whereas the T variant induced a 79% mean increase in blood levels among heterozygous (CT) and 100% among homozygous (TT) recipients. These results agreed with the mean levels in various recipient/donor populations, finding significant differences between them (P<.001 in CC vs CT and P<.01 in CT vs TT), as well as a certain influence of the donor genotype.
Fundación para la Investigación Hospital La Fe, Unidad Farmacogenética, Servicio Farmacia, Valencia, Spain. maria.jose.herrero@uv.es
M J
MJ
Herrero
L
L
Almenar
C
C
Jordán
I
I
Sánchez
J L
JL
Poveda
S F
SF
Aliño
D000704:Analysis of Variance; D016572:Cyclosporine / Q000627:therapeutic use*; D016027:Heart Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D016559:Tacrolimus / Q000627:therapeutic use*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus