CYP3A5*3 and CYP3A4*18 single nucleotide polymorphisms in a Chinese population.
BACKGROUND
Human cytochrome P450 3A evolved to catalyze the metabolism of numerous common therapy drugs and endogenous molecules. Members of the CYP3A are the majority expressed in human liver and intestine, and there are marked interindividual differences in their protein expression and activity. The activity of CYP3A enzyme in Chinese is highly variable, exceeding 14-fold, and contributes greatly to variation in oral bioavailability and systemic clearance of CYP3A substrates. The genetic factors play an important role in the interindividual variability in CYP3A activity. Detection of CYP3A5 and CYP3A4 variant alleles and knowledge about their allelic frequency in specific ethnic groups are important to lead to individualized drug dosing and improved therapeutics.


METHODS
We determined the allelic frequency of the CYP3A5*3 and CYP3A4*18 in a group of 302 Chinese subjects by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays.


RESULTS
In the group of 302 unrelated individuals, the frequency of the CYP3A5*3 and CYP3A4*18 variant allele in Chinese population were 0.778 (95% CI: 0.754, 0.802) and 0.01 (95% CI: 0, 0.02), respectively.


CONCLUSIONS
We developed a simple assay for the detection of the CYP3A4*18 allele and showed that in a Chinese population, CYP3A4*18 and CYP3A5*3 allelic frequencies are similar to that reported previously in Chinese resident in Taiwan. The frequency of the CYP3A5*3 allele in Chinese population is similar to the Japanese but lower than Caucasians. Meanwhile, our findings suggest that an approximate 62% of the Chinese population carrying CYP3A5*3/*3 genotype may appear not to express CYP3A5 protein.
Hu
Yong-Fang
YF
Pharmacogenetics Research Institute, Institute of Clinical Pharmacology, Central South University, Changsha, Hunan 410078, People's Republic of China.
He
Jun
J
Chen
Guo-Lin
GL
Wang
Dan
D
Liu
Zhong-Qi
ZQ
Zhang
Che
C
Duan
Li-Fang
LF
Zhou
Hong-Hao
HH
D000293:Adolescent; D000328:Adult; D000483:Alleles; D002681:China; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide
D003577:Cytochrome P-450 Enzyme System; C104464:CYP3A protein, human; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human