Identification of a novel variant CYP2C9 allele in Chinese.
Article Details
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Si D, Guo Y, Zhang Y, Yang L, Zhou H, Zhong D
Identification of a novel variant CYP2C9 allele in Chinese.
Pharmacogenetics. 2004 Jul;14(7):465-9.
- PubMed ID
- 15226678 [ View in PubMed]
- Abstract
OBJECTIVES: 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. CONCLUSION: This study suggests that this novel CYP2C9 allele was correlated with reduced plasma clearance of drugs that are substrates for CYP2C9.
DrugBank Data that Cites this Article
- Pharmaco-genomics
Drug Interacting Gene/Enzyme Allele name Genotypes Defining change(s) Type(s) Description Details Phenytoin Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712CYP2C9*13 Not Available - 269T>C (rs72558187)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Celecoxib Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712CYP2C9*13 Not Available - 269T>C (rs72558187)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Warfarin Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712CYP2C9*13 Not Available - 269T>C (rs72558187)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Clopidogrel Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712CYP2C9*13 Not Available - 269T>C (rs72558187)
Effect Inferred Poor drug metabolizer, lower dose requirements, higher risk for drug-drug interactions Details Acetylsalicylic acid Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712CYP2C9*13 Not Available - 269T>C (rs72558187)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Glipizide Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712CYP2C9*13 Not Available - 269T>C (rs72558187)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Tolbutamide Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712CYP2C9*13 Not Available - 269T>C (rs72558187)
Effect Inferred Poor drug metabolizer, lower dose requirements Details Acenocoumarol Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712CYP2C9*13 Not Available - 269T>C (rs72558187)
Effect Inferred Poor drug metabolizer, associated with lower dose requirement. Details Phenprocoumon Cytochrome P450 2C9
Gene symbol: CYP2C9
UniProt: P11712CYP2C9*13 Not Available - 269T>C (rs72558187)
ADR Inferred Associated with delayed stabilization. If carrier of rs9934438 as well, increased risk of severe overanticoagulation. Details