title: Genotype frequencies of VKORC1 and CYP2C9 in native and Mestizo populations from Mexico, potential impact for coumarin dosing.
abstract: 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.
authors.affiliation: Laboratorio de Diagnostico Genomico, Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Villegas-Torres
authors.affiliation: Laboratorios Medicos Polanco, Sofocles 145, Col. Polanco, 11550 Mexico D.F., Mexico.
authors.forename: Francisco
authors.initials: F
authors.lastname: Sánchez-Girón
authors.affiliation: Conjunto Lar de México S.A. de C.V. Bolivar, Col. Alamos 03400 Mexico D.F., Mexico.
authors.forename: Karla
authors.initials: K
authors.lastname: Jaramillo-Villafuerte
authors.affiliation: Laboratorio de Farmacogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Periferico Sur 4809, Col. Arenal Tepepan, 14610 Mexico City, Mexico.
authors.forename: Xavier
authors.initials: X
authors.lastname: Soberón
authors.affiliation: Laboratorio de Farmacogenómica, Instituto Nacional de Medicina Genómica (INMEGEN), Periferico Sur 4809, Col. Arenal Tepepan, 14610 Mexico City, Mexico. Electronic address: vgonzalez@inmegen.gob.mx.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Gonzalez-Covarrubias
mesh_terms: D003374:Coumarins / Q000008:administration & dosage* / Q000493:pharmacokinetics; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D054796:Drug Dosage Calculations; D005006:Ethnicity / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D008800:Mexico / Q000208:ethnology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*
chemical_list: D003374:Coumarins; C030123:coumarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9; Mexican populations; VKORC1