Villegas-Torres Beatriz, Sánchez-Girón Francisco, Jaramillo-Villafuerte Karla, Soberón Xavier, Gonzalez-Covarrubias Vanessa
Laboratorio de Diagnostico Genomico, Instituto Nacional de Medicina Genómica (INMEGEN), México City, Mexico.
Laboratorios Medicos Polanco, Sofocles 145, Col. Polanco, 11550 Mexico D.F., Mexico.
Gene. 2015 Mar 10;558(2):235-40. doi: 10.1016/j.gene.2014.12.068. Epub 2015 Jan 2.
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.
墨西哥人群中药理学基因变异的收集工作仍不完整，因此，我们旨在对一千多名个体中CYP2C9和VKORC1基因上11个单核苷酸多态性（SNP）的基因型频率进行特征分析，并探讨它们对香豆素剂量的潜在影响。在原住民中，基因型频率表明超过92%的人会表现出广泛代谢。对于混血人群，CYP2C9广泛代谢者（79%）、中间代谢者（20.0%）和慢代谢者（1.0%）的比例与原住民有显著差异，且在墨西哥不同州之间有所不同。VKORC1基因上7个SNP的基因型频率在原住民和混血人群中分布更为均匀。VKORC1单倍型分析显示，大多数原住民可分为单倍型H1或H7 - H8，而混血人群中其他单倍型的频率分布更广。我们的观察结果证实了之前关于主要CYP2C9等位基因基因型分布的报道，并有助于收集相关VKORC1变异的基因型频率。
