Objective: To investigate the polymorphisms of CYP3A5 gene in Chinese population and the association between CYP3A5 genotypes and their clinical functions.
Methods: CYP3A5 gene varisances were detected in 180 samples using denaturing high-performance liquid chromatography(DHPLC), and CsA concentrations in 12 of 180 samples from hemopoietic stem cell transplant recipients were monitored by a commercial fluorescence polarization immunoassay. The data were analyzed by a statistical software.
Results: In the 180 samples, there was only one allelic variant CYP3A5*3 with a frequency of 76.1% (274/360), and there were three CYP3A5 genotypes, namely CYP3A5*1/*1, CYP3A5*1/*3 and CYP3A5*3/*3 with frequencies of 5.6%, 36.7% and 57.8% respectively. Also, there were significant differences in CsA concentrations, including standardized trough concentrations C(0) and two-hour peak concentrations C(2), between CYP3A5 CYP3A5*1/*1 and CYP3A5*1/*3 found in 12 hemopoietic stem cell transplant recipients, and both C(0) and C(2) in CYP3A5*1/*1 were lower than those in CYP3A5*1/*3.
Conclusion: CYP3A5*3 is the primary allelic variant in Chinese population. CYP3A5 genotypes are closely associated with blood CsA concentrations in hemopoietic stem cell transplant recipients, and CYP3A5*1/*1 requires a larger CsA dose to maintain the same blood concentration than does CYP3A5*1/*1. CYP3A5 genotyping by DHPLC may predict recipients' phenotype and CsA dose requirement.
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