Influence of pharmacogenetic polymorphisms in routine immunosuppression therapy after renal transplantation.
Pharmacogenetics is the study of the cause of various individual responses to the same pharmacologic therapy. Genetic alterations in a single nucleotide in the genes responsible for transport and metabolism of an immunosuppression drug may modify patient response. Although pharmacogenetics is of interest, its clinical relevance remains to be demonstrated. The objective of the present study was to evaluate the effect of single-nucleotide polymorphisms (SNPs) in renal transplant recipients and their donors relative to blood concentrations of tacrolimus in the first 2 weeks posttransplantation. Seventy-one blood samples each from renal transplant recipients and their donors were analyzed using a genetic analysis system (MassARRAY; Sequenom, Inc, San Diego, California) in an attempt to characterize the more relevant SNPs of the ABCB1 and CYP3A5 genes for correlation with recipient trough concentrations of drug. Two-way analysis of variance and Bonferroni post hoc tests were used. In agreement with theoretical predictions, the wild-type genotype in ABCB1 SNPs (CC) tended to stabilize drug concentrations within the therapeutic range, whereas the T variant induced a mean increase in blood concentrations of more than 60%. These findings are in agreement with statistical tests that compared mean concentrations in various recipient-donor populations and found significant differences between them (P<.001) in CC vs TT, and P<.01 in CT vs TT). Donor genotype did not seem to be relevant. However, further studies are required to achieve more robust conclusions.
Herrero
M J
MJ
Fundación para la Investigación Hospital La Fe, Unidad Farmacogenética, Servicio Farmacia, Valencia, Spain. maria.jose.herrero@uv.es
Sánchez-Plumed
J
J
Galiana
M
M
Bea
S
S
Marqués
M R
MR
Aliño
S F
SF
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016030:Kidney Transplantation; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A