Influence of CYP3A5 polymorphism on tacrolimus blood concentrations in renal transplant patients |
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Authors: | Nie Xin-min Gui Rong Zhao Hong-shan Ma Da-long Li Deng-qing Yuan Hong and Huang Zu-fa |
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Affiliation: | (1) The Third Xiangya Hospital, Central South University, 410013 Changsha, China;(2) Center for Human Disease Genomics of Peking University, 100083 Beijing, China |
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Abstract: | Objective Tacrolimus is an immunosuppressive drug with narrow therapeutic range and wide interindividual variation in its pharmacokinetics.
Tacrolimus is a substrate of cytochrome P450(CYP)3A5. The aim of this study was to evaluate whether the A6986G polymorphism
is associated with tacrolimus concentration /dose ratio. Methods Fifty-two Chinese renal transplant patients were enrolled in this study. Their body weight, dosage and concentration of tacrolimus
were observed. CYP3A5 genotype was determined by polymerase chain reaction followed by restriction fragment length polymorphism
analysis. Results A significant association was found between tacrolimus levels per dose/kg/d and CYP3A5 gene A6986G polymorphism (P<0.001). The CYP3A5 * 3 * 3 patients have a significantly higher tacrolimus level/dose than CYP3A5 * 1 * 1 and CYP3A5 * 1
* 3. Conclusions CYP3A5 gene A6986G polymorphism is associated with tacrolimus pharmacokinetics and dose requirements. Pharmacogenetic methods
could be employed prospectively to help the dose selection and to individualize immunosuppressive therapy according to the
result.
Foundation item: Project (03GZ3072) supported by the Science and Technology Department of Hunan Province; project (2004035206) supported by
the China Postdoctoral Foundation and project (30300383) supported by the National Natural Sciences Foundation of China |
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Keywords: | tacrolimus gene polymorphism CYP3A5 |
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