CYP2D6 genotype and phenotype determination in a Mexican Mestizo population

Objective: Although CYP2D6 genetic polymorphism plays an important role in interindividual and interethnic variability in drug response, very few pharmacogenetic data are available from Hispanic populations, including Mexicans. For this purpose, this study was undertaken to determine CYP2D6 genotype and phenotype in a healthy Mexican Mestizo population. Methods: Genotyping of five CYP2D6 mutant alleles by PCR-RFLP, and CYP2D6*5 and duplicated CYP2D6 alleles by long-PCR was performed in two hundred and forty three Mexican Mestizos. Of these, one hundred subjects were also phenotyped using dextromethorphan as the probe drug. Results: The frequency of CYP2D6*2, *3, *4, *5, *10, *17 was 19.34%, 1.44%, 11.21%, 2.67%, 12.45%, and 1.65%, respectively, while duplicated CYP2D6 alleles were found in 12.76% of the 243 genotyped subjects. Among the 100 phenotyped subjects, we identified ten (10%, 95% confidence interval of 4.12-15.9) individuals as poor metabolizers by using the published antimode for Caucasians. The mean log(10) dextromethorphan/dextrorphan ratio of the total sample was -2.05. The mean (SD) of the log(10) MR in the CYP2D6 subgroups was UM=-2.6 (0.86); EM=-2.09 (0.98); IM=-1.71 (1.06); and PM=0.42 (0.625). These data show a trend toward a smaller mean log MR (higher enzyme activity) as the number of active alleles increases. Conclusions: The PM frequency of CYP2D6 in the population studied was 10%, which is very similar to Spanish Caucasians. The observed frequency of the CYP2D6 alleles tested was unique for the Mexican Mestizo sample analyzed, and in accordance to the Caucasian, Asian and African admixture in this population.