Genotype frequencies of VKORC1 and CYP2C9 in Native and Mestizo populations from Mexico, potential impact for coumarin dosing

• CYP2C9 genotype frequency differences between Mexican natives and Mestizos were significant.
• Common haplotypes for VKORC1 are reported for the first time in Native Mexicans.
• Haplotype distribution between natives and Mestizos differed significantly.
• CYP2C9 and VKORC1 genotypes are used to predict coumarin sensitivity in Mexicans.
• Findings contribute to define pharmacogenetic diversity in Mexican populations.

The collection of pharmacogenetic variants in Mexican populations remains incomplete, thus, we aimed to characterize the genotype frequency of 11 SNP on CYP2C9 and VKORC1 in more than one-thousand individuals, and to explore their potential impact on coumarin dosing. In natives, genotype frequencies indicate that over 92% would reflect an extensive metabolism. For Mestizo populations, the proportion of CYP2C9 extensive (79%), intermediate (20.0%) and poor metabolizers (1.0%) was significantly different from that of natives, and varied among the different states of Mexico.Genotype frequencies of 7 SNP on VKORC1, were more homogenously distributed among natives and Mestizos. VKORC1 haplotype analysis revealed that most natives can be grouped into haplotypes H1 or H7–H8, while Mestizos showed a wider frequency distribution for other haplotypes. Our observations confirm previous reports on the genotype distribution of major CYP2C9 alleles, and contribute to the collection of genotype frequencies on relevant VKORC1 variants.