Differences between Spaniards and an Ecuadorian Mestizo population in CYP2C8, CYP2C9 and CYP2C19 polymorphisms. Comparison with other populations.

J Vicente1, A Soriano2, F Gonzalez-Andrade3, A Fanlo1, M Soria1, B Sinues1. 1University of Zaragoza, Pharmacology and Physiology 50009, Spain, 2University Hospital Miguel Servet, Rehabilitacion 50009, Spain, 3Central University of Ecuador, Faculty of Medical Sciences 170136, Ecuador

The polymorphisms of the P450 isoenzymes (CYPs) 2C9, 2C8 and 2C19 deal to important interindividual and interethnic variability in the metabolism of many important drugs and hence in their clinical response. However, no studies have examined the frequency distribution of the major variants alleles of the genes coding such isoenzymes among the Ecuadorian Mestizo people which is the most largest group in Ecuador. The present study was designed to investigate the potential differences between Ecuadorian Mestizo people and Spaniards regarding CYP2C9*2, CYP2C9*3, CYP2C8*3, CYP2C19*2 and CYP2C19*3 variant alleles and also to compared the observed frequencies with those previously reported in different ethnic groups. DNA from 297 Ecuadorian Mestizo and 282 Spaniard subjects were analyzed by DNA pyrosequencing method. The allelic frequencies for CYP2C9*2 and CYP2C9*3 in Ecuadorian Mestizo subjects (0.5% and 3.7%, respectively) were significantly lower than those found in Spaniards (13.3%, p<0.001 and 7.7%, p<0.05, respectively). CYP2C8*3, which was in linkage disequilibrium with CYP2C9*2, was detected in a lower frequency in Ecuadorian (6.5%) than in Spaniards (11.4%) (p<0.001). With regard to the CYP2C19 variants, while CYP2C19*2 was also less frequent among Ecuadorian Mestizo people (7.8%) than among Spaniards (12.8%) (p<0.01), no differences were observed in the frequency of the CYP2C19*3 (p>0.05) between both populations. The comparison between the allele frequencies studied here and those reported for other populations, clearly provide further evidence of ethnic heterogeneity in CYP2C polymorphisms and also reinforce the notion about the biracial origin of the Mestizo population from Ecuador. The findings of this study could contribute to better clinical care of Mestizo population from Ecuador and should be considered in allele disease association studies