[Study on polymorphisms of CYP3A5 gene and their clinical role].
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.


CONCLUSIONS
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.
Wang
Han-ping
HP
Department of Hematology, the First Municipal People's Hospital of Guangzhou, Guangzhou, Guangdong, 510180 PR China. wanghanping@21cn.net
Xie
Jian-jin
JJ
Zhang
Ze-yun
ZY
Ying
Yi
Y
Zhu
Zhi-gang
ZG
Mao
Ping
P
D002851:Chromatography, High Pressure Liquid; D016572:Cyclosporine / Q000097:blood; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D016231:Fluorescence Polarization Immunoassay; D005787:Gene Frequency; D005838:Genotype; D006412:Hematopoietic Stem Cells / Q000166:cytology; D006801:Humans; D011110:Polymorphism, Genetic; D033581:Stem Cell Transplantation / Q000379:methods*
D016572:Cyclosporine; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A