Rapid detection of the known SNPs of CYP2C9 using oligonucleotide microarray.
OBJECTIVE
Cytochrome P450 2C9 (CYP2C9) is a polymorphic enzyme responsible for the metabolism of a large number of clinically important drugs. Individuals with mutant enzymes may risk serious side effects under routine therapy with certain drugs metabolized by CYP2C9. In order to facilitate the detection of the known SNPs of CYP2C9, an allele-specific oligonucleotide (ASO) based microarray was made.


METHODS
An oligonucleotide microarray was made to facilitate the SNP (single nucleotide polymorphism) screening and was applied for the detection of CYP2C9 polymorphism in 62 high blood pressure (HBP) patients who received Irbesartan for treatment. Part of the genotyping results was confirmed by direct sequencing. And the relation between CYP2C9 polymorphism and therapeutic outcome of Irbesartan was statistically analyzed.


RESULTS
Heterozygous alleles of CYP2C9*1/*3 were found in 7 out of 62 subjects. No mutant alleles of CYP2C9*2, *4 and *5 and no homozygous mutant alleles were detected. The 7 heterozygous CYP2C9*1/*3 and 13 random wild type DNA samples were subjected to direct sequencing with purified PCR products and same genotyping results were obtained with the 20 DNA samples. There was no significant difference in the odds of effectiveness of Irbesartan between the wild type (normal) group and CYP2C9*1/*3 (mutant) group (P>0.05).


CONCLUSIONS
The oligonucleotide microarray made in this study is a reliable assay for detecting the CYP2C9 known alleles and the heterozygous CYP2C9*1/*3 has no significant effects on the therapeutic outcome of Irbesartan.
Wen
Si-Yuan
SY
Beijing Institute of Radiation Medicine, No. 27 Taiping Road, Beijing 100850, China. sqwang@nic.bmi.ac.cn
Wang
Hui
H
Sun
Ou-Jun
OJ
Wang
Sheng-Qi
SQ
D000483:Alleles; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001713:Biphenyl Compounds / Q000627:therapeutic use; D065729:Cytochrome P-450 CYP2C9; D006579:Heterozygote; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics*; D000077405:Irbesartan; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D013777:Tetrazoles / Q000627:therapeutic use; D013997:Time Factors
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000077405:Irbesartan