Losartan hydroxylation phenotype in an Ecuadorian population: influence of CYP2C9 genetic polymorphism, habits and gender

Pharmacogenomics. 2012 Nov;13(15):1711-7. doi: 10.2217/pgs.12.160.

Abstract

Aim: To describe for the first time CYP2C9 hydroxylation phenotype with CYP2C9 genotypes in a Hispanic (Ecuadorian) population using losartan; and the relevance of gender, tobacco, ethanol and caffeine consumption on the enzyme hydroxylation capacity.

Methods: Ecuadorian healthy volunteers (n = 194) received a single oral dose of 25 mg losartan. Losartan metabolic ratio was defined as losartan:E3174 concentration. CYP2C9 alleles *2, *3, *4, *5 and *6 were analyzed.

Results: No phenotypically poor metabolizers were found. The metabolic ratio (mean ± standard deviation) was higher (p < 0.05) in CYP2C9*1/*3 carriers (12.4 ± 13.8; n = 6) versus CYP2C9*1/*1 (4.9 ± 7.0; n = 167), as well as in females versus males (6.72 ± 9.72 and 3.76 ± 4.48, respectively; p < 0.05). Only the following genotypes, CYP2C9*1/*1, CYP2C9*1/*2 and CYP2C9*1/*3, were found with a frequency of 86.1%, 10.8% and 3.1%, respectively.

Conclusion: Despite the mean metabolic ratio being higher in this population than in others previously studied across genotypes, no poor metabolizers, either phenotypically or genotypically, were found.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alcohol Drinking / genetics
  • Alcohol Drinking / metabolism
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Caffeine / administration & dosage
  • Coffee
  • Cytochrome P-450 CYP2C9
  • Female
  • Genotype
  • Habits
  • Hispanic or Latino / genetics*
  • Humans
  • Hydroxylation
  • Losartan / metabolism*
  • Male
  • Phenotype
  • Polymorphism, Genetic
  • Sex Factors
  • Smoking / genetics
  • Smoking / metabolism
  • Young Adult

Substances

  • Coffee
  • Caffeine
  • CYP2C9 protein, human
  • Cytochrome P-450 CYP2C9
  • Aryl Hydrocarbon Hydroxylases
  • Losartan