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

Objective: To search for ethnic variability in the impact of cytochrome P-450 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.