Relationship between the CYP2C9 IVS8-109A>T polymorphism and high losartan hydroxylation in healthy Ecuadorian volunteers

Pharmacogenomics. 2014 Aug;15(11):1417-21. doi: 10.2217/pgs.14.85.

Abstract

Aim: 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.

Results: 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%).

Conclusion: 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.

Keywords: CYP2C9; IVS8-109A>T; intronic polymorphism; losartan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Antihypertensive Agents / therapeutic use*
  • Cytochrome P-450 CYP2C9 / genetics*
  • Female
  • Genotype
  • Hispanic or Latino / genetics
  • Humans
  • Hydroxylation / genetics*
  • Losartan / therapeutic use*
  • Male
  • Polymorphism, Genetic / genetics*
  • White People / genetics*
  • Young Adult

Substances

  • Antihypertensive Agents
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Losartan