High frequency of mutations related to impaired CYP2C9 metabolism in a Caucasian population

Eur J Clin Pharmacol. 2001 Apr;57(1):47-9. doi: 10.1007/s002280100264.

Abstract

Objective: To search for ethnic variability in the impact of cytochrome P450 2C9 (CYP2C9) polymorphism.

Methods: CYP2C9 allelic variants related to impaired CYP2C9 metabolism were analysed in genomic DNA from 157 Spanish healthy subjects using amplification-restriction and sequencing procedures.

Results: The frequency for CYP2C9 mutated alleles is higher among the Spanish subjects analysed than that reported for other Caucasian individuals: CYP2C9*2, 0.143 and CYP2C9*3, 0.162 (P = 0.0001). Nearly 10% of the individuals studied are expected to metabolise deficiently CYP2C9 substrates.

Conclusion: In some Caucasian populations the impact of the CYP2C9 polymorphism may be much higher than that estimated from genotyping studies published to date.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aryl Hydrocarbon Hydroxylases*
  • Chi-Square Distribution
  • Confidence Intervals
  • Cytochrome P-450 CYP2C9
  • Cytochrome P-450 Enzyme System / genetics*
  • Cytochrome P-450 Enzyme System / metabolism*
  • Gene Frequency / genetics*
  • Genotype
  • Humans
  • Middle Aged
  • Mutation / genetics*
  • Steroid 16-alpha-Hydroxylase*
  • Steroid Hydroxylases / genetics*
  • Steroid Hydroxylases / metabolism*
  • White People / genetics*

Substances

  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Steroid 16-alpha-Hydroxylase