title: Relationship between the CYP2C9 IVS8-109A>T polymorphism and high losartan hydroxylation in healthy Ecuadorian volunteers.
abstract: OBJECTIVE
  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%).
  
  
  CONCLUSIONS
  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.
authors.affiliation: CICAB Clinical Research Centre, Extremadura University Hospital & Medical School, Servicio Extremeño de Salud, Badajoz 06080, Spain.
authors.forename: Pedro
authors.initials: P
authors.lastname: Dorado
authors.forename: Alicia
authors.initials: A
authors.lastname: Gallego
authors.forename: Eva
authors.initials: E
authors.lastname: Peñas-LLedó
authors.forename: Enrique
authors.initials: E
authors.lastname: Terán
authors.forename: Adrián
authors.initials: A
authors.lastname: LLerena
mesh_terms: D000328:Adult; D000483:Alleles; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D006900:Hydroxylation / Q000235:genetics*; D019808:Losartan / Q000627:therapeutic use*; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: D000959:Antihypertensive Agents; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D019808:Losartan
keywords: CYP2C9; IVS8-109A>T; intronic polymorphism; losartan