CICAB Clinical Research Centre, Extremadura University Hospital and Medical School, Badajoz, Spain.
Pharmacogenomics J. 2011 Apr;11(2):108-12. doi: 10.1038/tpj.2010.29. Epub 2010 May 11.
Earlier we had found that the CYP2C92 allelic frequency was lower in Mexican-Americans living in California than in Spaniards (SP). This was assumed to be related to the low CYP2C92 and 3 allele frequencies in Orientals. This study was therefore aimed at analyzing whether there were also differences in CYP2C9 allele frequencies between Mexican-Tepehuanos (MT) and Mexican-Mestizos (MM) living in northwestern Mexico and SP. The CYP2C92 frequency was expected to be lower in the indigenous MT than in the two other groups, and lower in MM than in SP as in our earlier study. CYP2C9 genotypes and allele frequencies of two populations of healthy volunteers, MT (n=99) and MM (n=102), were compared with a population of SP (n=327). The data were also compared with our previously published population of Mestizo-Mexican-Americans (MA). The CYP2C9 genotypes among the studied populations were in equilibrium. The frequencies of CYP2C92 were 0.01, 0.07, 0.08, and 0.16 for MT, MM, MA, and SP subjects, respectively. In agreement with our hypothesis, CYP2C92 was significantly lower in the Mexican populations than in the SP (P<0.05), and among Mexicans in the MT than in the MM and MA groups (P<0.05), which presented similar frequencies. Moreover, the frequency of CYP2C93 was found to be lower (P<0.05) in MM (0.015) and MT (0.015) than in MA (0.06) and SP (0.08). Finally, the CYP2C96 allele was present just in one MM subject, and CYP2C94 and 5 were not found in the studied populations. Therefore, these findings add further evidence about CYP2C9 genetic diversity within Hispanic populations with regard to their ancestry. Considering that CYP2C92 and CYP2C93 alleles have altered catalytic activities relative to CYP2C9*1, the present data suggest the need for pharmacogenetic studies to optimize drug dosages in different populations.
先前我们发现,生活在加利福尼亚州的墨西哥裔美国人中 CYP2C92 等位基因频率低于西班牙人(SP)。这被认为与东方人 CYP2C92 和3 等位基因频率较低有关。因此,本研究旨在分析生活在墨西哥西北部的特佩瓦诺人(MT)和墨西哥裔混血儿(MM)与 SP 之间 CYP2C9 等位基因频率是否存在差异。预计 CYP2C92 在土著 MT 中的频率低于其他两组,在 MM 中的频率低于 SP,与我们之前的研究一致。比较了两组健康志愿者 MT(n=99)和 MM(n=102)的 CYP2C9 基因型和等位基因频率与 SP 组(n=327)。数据还与我们之前发表的墨西哥裔美国裔混合人群(MA)进行了比较。研究人群中的 CYP2C9 基因型处于平衡状态。研究人群 CYP2C92 的频率分别为 MT 为 0.01、0.07、0.08 和 0.16,MM 为 0.07、0.08、0.16 和 0.16,MA 为 0.07、0.08、0.16 和 0.16,SP 为 0.01、0.08、0.16 和 0.16。与我们的假设一致,CYP2C92 在墨西哥人群中的频率明显低于 SP(P<0.05),在墨西哥人中 MT 组明显低于 MM 和 MA 组(P<0.05),这两组的频率相似。此外,MM(0.015)和 MT(0.015)中的 CYP2C93 频率明显低于 MA(0.06)和 SP(0.08)(P<0.05)。最后,仅在一个 MM 受试者中发现了 CYP2C96 等位基因,而在研究人群中未发现 CYP2C94 和5。因此,这些发现进一步证明了西班牙裔人群中 CYP2C9 遗传多样性与其祖先有关。鉴于 CYP2C92 和 CYP2C93 等位基因相对于 CYP2C9*1 的催化活性发生了改变,目前的数据表明需要进行药物遗传学研究,以优化不同人群的药物剂量。