Identification of a novel variant CYP2C9 allele in Chinese.
OBJECTIVE
Cytochrome P450 (CYP) 2C9 metabolizes about 16% of drugs in current clinical use, including lornoxicam and tolbutamide. SNPs in the CYP2C9 gene have increasingly been recognized as determinants of the metabolic phenotype that underlies interindividual and ethnic differences.


METHODS
The present study focused on a Chinese poor metabolizer (PM) whose apparent genotype (CYP2C9*1/CYP2C9*3) did not agree with his PM phenotype for both lornoxicam and tolbutamide. By sequencing his CYP2C9 gene, we identified a new variant CYP2C9 allele involving a T269C transversion in exon 2 that leads to a Leu90Pro substitution in the encoded protein.


RESULTS
The CYP2C9 genotype analysis in the family of the poor metabolizer showed the new exon 2 change and CYP2C9*3 occurred on different alleles. Thus, the PM status of this subject could be attributed to his being heterozygous for the CYP2C9 T269C allele together with the CYP2C9*3. Frequency analysis in 147 unrelated Chinese males indicated approximately 2% of the Chinese population carry the allele.


CONCLUSIONS
This study suggests that this novel CYP2C9 allele was correlated with reduced plasma clearance of drugs that are substrates for CYP2C9.
Si
Dayong
D
College of Life Science, Jilin University, Changchun, China.
Guo
Yingjie
Y
Zhang
Yifan
Y
Yang
Lei
L
Zhou
Hui
H
Zhong
Dafang
D
D020413:3' Untranslated Regions / Q000235:genetics; D020121:5' Untranslated Regions / Q000235:genetics; D000483:Alleles; D019943:Amino Acid Substitution; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D065729:Cytochrome P-450 CYP2C9; D005091:Exons / Q000235:genetics; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D013379:Substrate Specificity
D020413:3' Untranslated Regions; D020121:5' Untranslated Regions; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases