CICAB Clinical Research Centre, Extremadura University Hospital & Medical School, Servicio Extremeño de Salud, Badajoz 06080, Spain.
Pharmacogenomics. 2014 Aug;15(11):1417-21. doi: 10.2217/pgs.14.85.
The CYP2C9 IVS8-109T allele was recently found to be more frequent among Swedish individuals, who have the highest losartan metabolic ratio (MR; losartan:E-3174). Thus, the influence of the CYP2C9 IVS8-109A>T polymorphism on the losartan MR was evaluated among healthy Ecuadorians. In addition, the frequency of the CYP2C9 IVS8-109A>T polymorphism was determined.
Among CYP2C9-homozygous wild-types, those with the CYP2C9 IVS8-109T/T versus A/A genotypes had a lower MR (p < 0.05). Furthermore, the frequency of the CYP2C9 IVS8-109T variant was lower in Ecuadorians (21.4%; p < 0.001) than in populations from Sweden or Asia (ranging from 32 to 46%).
In this Ecuadorian population, the CYP2C9 IVS8-109T allele was associated with an increased CYP2C9 hydroxylation capacity. Further investigation needs to be carried out in order to clarify the relevance of the SNP of CYP2C9 IVS8-109A>T on losartan hydroxylation across populations and its potential implications in CYP2C9 activity.
最近发现，CYP2C9 IVS8-109T 等位基因在瑞典人群中更为常见，而瑞典人群的氯沙坦代谢比（MR；氯沙坦：E-3174）最高。因此，评估了 CYP2C9 IVS8-109A>T 多态性对健康厄瓜多尔人氯沙坦 MR 的影响。此外，还确定了 CYP2C9 IVS8-109A>T 多态性的频率。
在 CYP2C9 纯合野生型中，CYP2C9 IVS8-109T/T 与 A/A 基因型的个体 MR 较低（p < 0.05）。此外，厄瓜多尔人群 CYP2C9 IVS8-109T 变异型的频率低于瑞典或亚洲人群（范围为 32%至 46%）（p < 0.001）。
在厄瓜多尔人群中，CYP2C9 IVS8-109T 等位基因与 CYP2C9 羟化能力增加相关。需要进一步研究以阐明 CYP2C9 IVS8-109A>T SNP 在不同人群中对氯沙坦羟化的相关性及其对 CYP2C9 活性的潜在影响。
