Distribution of potential risk alleles and haplotypes of the CYP2C9 and CYP2C19 genes in Mexican native populations: A comparative study among Amerindian populations

Abstract Objectives Mexico harbours a very complex genetically diverse population composed of two main groups: Mexican Mestizos and at least 68 heterogeneous native Mexican populations. CYP2C9 and CYP2C19 polymorphisms may confer risk for specific adverse drug reactions and therapeutic effect failure, and their frequencies exhibit ethnic variability. We aimed to describe the distribution of CYP2C9 and CYP2C19 alleles and haplotypes in four Mexican indigenous populations and to compare data with those reported for other native Mexican and Amerindian populations. Methods We genotyped 459 DNA samples from healthy individuals of four native Mexican populations: Yaqui, Mixteco, North Lacandon and South Lacandon for CYP2C9*2 and CYP2C9*3 alleles using a TaqMan qPCR allelic discrimination assay, and CYP2C19*2 and CYP2C19*3 alleles using polymerase chain reaction–restriction fragment length polymorphisms (PCR–RFLP). Results Frequencies were in the range 0.7–2.4% for the CYP2C9*2 allele and 0.5–7.8% for the CYP2C9*3 allele. The CYP2C19*2 allele was found in a high frequency (range, 6.0–19.3%), while CYP2C19*3 was not found. Haplotype G A CA ( CYP2C19*2–CYP2C9*1 ), which harbours the loss-function allele CYP2C19*2 , was observed in almost all populations studied, in the range 5.9–19.3%. Genetic variability was observed mainly between northern and southern populations, both among our studied populations and among other native populations of Mexico and other Amerindians ( p Conclusion This study highlights the genetic variability of the Mexican native population and, because the CYP2C19*2 allele was the most frequent in almost all our studied populations, also draws attention to the potential clinical impact of this allele in vulnerable and isolated groups such as native populations of Mexico.