Polimorfismos de relevancia farmacogenética de las familias 1A2, 2C y 3A en población indígena del noroeste de México

Zusammenfassung

In Mexico inhabit more than 62 Native Amerindian groups, whose genetic background is different to the Mexican Mestiza population. Therefore, it is difficult to clearly infer their expected drugs response. The distribution of polymorphisms with functional implications in CYP450 enzymes, will determine the risk of toxicity or therapeutic failure in these populations. The aim of this study was to determine the frequency of polymorphisms in genes CYP1A2, CYP2C9/19 and CYP3A4, in eight indigenous populations from Northwest Mexico. A total of 506 indigenous were genotyped for the CYP1A2*1F, CYP2C9*2, *3 and *6, CYP2C19*2 and *3, and CYP3A4*1B, by PCR-RFLP assay and real-time PCR. Additionally, was to performed molecular evaluation of ancestry by 15 STRs markers. The frequencies for CYP1A2*1F were of 0.53 - 0.92. CYP2C9*2 was found only in Seris (0.026) and Mayos (0.057) indigenous groups, and was dependent on the European ancestral component. The frequency of CYP2C9*3 allele was 0 - 0.104. The CYP2C19*2 variant was found in range of 0.026 - 0.433. CYP2C9*6 and CYP2C19*3 were not detected in this study. CYP3A4*1B was detected with a frequency of 0 - 0.115. The allelic frequencies of CYP450 were different from those described in Mexican Mestizo and Asian population. These results have important therapeutic implications that should be considered for drug optimization in Mexican indigenous population.