Impact of CYP3A5 genetic polymorphism on cross-reactivity in tacrolimus chemiluminescent immunoassay in kidney transplant recipients.
BACKGROUND
Tacrolimus immunoassays possess cross-reactivity with metabolites in the blood. The aim of this study was to evaluate the cross-reactivity in tacrolimus chemiluminescent immunoassay (CLIA) in kidney transplant recipients and to characterize the cross-reactivity according to CYP3A5 genetic polymorphism.


METHODS
The subjects were 50 kidney transplant recipients receiving low-dose tacrolimus. Blood levels of tacrolimus at 12h (C(12)) measured by CLIA were compared with that by LC-MS/MS using Bland-Altman analysis. The influence of CYP3A5 genotypes on the cross-reactivity in tacrolimus CLIA was evaluated by interaction plots.


RESULTS
No significant difference was observed in tacrolimus C(12) between the CYP3A5*1/*3 and CYP3A5*3/*3 genotypes. The dose-normalized C(12) of tacrolimus was significantly higher in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. The C(12) ratio of 13-O-demethylate to tacrolimus was significantly lower in the CYP3A5*3/*3 genotype than in the CYP3A5*1/*3 genotype. Tacrolimus C(12) measured by CLIA was 35% higher than that by LC-MS/MS. A higher cross-reactivity was observed in the patients with a tacrolimus C(12) of less than 3 μg/l and CYP3A5*1/*3 genotype.


CONCLUSIONS
This study confirmed the cross-reactivity in CLIA in kidney transplant recipients receiving low-dose tacrolimus. High metabolic capacity associated with the CYP3A5*1 genotype affected the cross-reactivity in patients with low tacrolimus levels.
Department of Hospital Pharmacy, Hamamatsu University School of Medicine, 1-20-1 Handayama, Higashi-ku, Hamamatsu, Shizuoka 431-3192, Japan.
Kumi
K
Hirano
Takafumi
T
Naito
Yasuaki
Y
Mino
Tatsuya
T
Takayama
Seiichiro
S
Ozono
Junichi
J
Kawakami
D000328:Adult; D003429:Cross Reactions; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007118:Immunoassay; D007166:Immunosuppressive Agents / Q000097:blood* / Q000737:chemistry / Q000378:metabolism; D016030:Kidney Transplantation; D008163:Luminescent Measurements; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D016559:Tacrolimus / Q000097:blood* / Q000737:chemistry / Q000378:metabolism
D007166:Immunosuppressive Agents; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; D016559:Tacrolimus