CYP2D6 polymorphism in a Mexican American population.

BACKGROUND

Pharmacogenetic data are largely unavailable for Mexican Americans, despite being one of the largest populations in America.

METHODS

The CYP2D6 genotype (n = 349) and dextromethorphan hydroxylation phenotype (n = 285) were studied in 380 Mexican American subjects from Los Angeles County.

RESULTS

The allelic frequency was 22.8% for CYP2D62, 10.3% for CYP2D64, 7.4% for CYP2D610, 2.3% for CYP2D65, 1% for CYP2D6XN (duplication), and <1% for CYP2D63 and CYP2D617. By using the published antimode for Caucasians, we identified nine subjects as poor metabolizers, an incidence of 3.2%. Of the eight poor metabolizers who were also genotyped, five either were homozygous for the CYP2D64 allele (4 cases) or had a combination of CYP2D64 and CYP2D65 alleles. The mean log(10) dextromethorphan/dextrorphan ratio was -2.47 for those classified as extensive metabolizers. The number of functional alleles among the extensive metabolizers correlated strongly with the phenotype, suggesting a gene-dose effect.

CONCLUSION

Compared with previous reports on Caucasian populations, studies show that Mexican Americans appear to possess a lower rate of CYP2D6*4. Frequencies for the other alleles appear to be less divergent between the two groups. This genotypic pattern might be responsible for the lower rate for the poor metabolizer status, as well as for the faster enzyme activity in the extensive metabolizer subjects that was also reflected in our data.