Genetic polymorphism of cytochrome P4502C19 in Mexican Americans: A cross-ethnic comparative study

Objectives. Our objectives were to investigate cytochrome P450 (CYP) 2C19 polymorphism in Mexican Americans and compare the findings with those in 4 other ethnic groups. Methods: The CYP2C19 genotype (n = 346) and S-mephenytoin hydroxylation phenotype (n = 220) were studied in a Mexican American population from Los Angeles County. Another 4 ethnic groups, African Americans (n = 236), whites (n = 273), East Asians (n = 161), and Southeast Asians (n = 80), were also recruited from Los Angeles County and genotyped and phenotyped for CYP2C19. Results. The frequencies of CYP2C19*2 and *3 were 9.7% and 0.1%, respectively, in Mexican Americans, which were lower than those of the other 4 ethnic groups, ranging from 12.7% to 31.2% and 0.8% to 9.6%, respectively (P <= .035). Seven Mexican American subjects were phenotyped as poor metabolizers. Thus the frequency of poor metabolizers in the Mexican American subjects was 3.2% (95% confidence interval, 0%-11.9%), which is similar to that of African Americans (5.4%) and whites (5.0%) and lower than that of East Asians (16.7%; P < .001) and Southeast Asians (23.9%; P < .001). Of the 7 poor metabolizers who were also genotyped, 2 were homozygous for the CYP2C19*2 alleles. CYP2C19*4, *5, *6, * 7, and *8 were studied and did not account for the unexplained finding. The number of functional alleles among the extensive metabolizers correlated with the phenotype, suggesting a gene-dosage effect in Mexican Americans. Conclusions. This is the first study to investigate CYP2C19 polymorphism in Mexican Americans. The frequencies of the CYP2C19*2 and *3 alleles in Mexican Americans were found to be significantly lower than in other ethnic groups. This genotypic pattern might be responsible for the lower rate of poor metabolizers in Mexican Americans compared with other ethnic groups.