Phenotype-genotype analysis of CYP2C19 in Colombian mestizo individuals.
BACKGROUND
Omeprazole is metabolized by the hepatic cytochrome P450 (CYP) 2C19 enzyme to 5-hydroxyomeprazole. CYP2C19 exhibits genetic polymorphisms responsible for the presence of poor metabolizers (PMs), intermediate metabolizers (IMs) and extensive metabolizers (EMs). The defective mutations of the enzyme and their frequencies change between different ethnic groups; however, the polymorphism of the CYP2C19 gene has not been studied in Colombian mestizos. The aim of this study was to evaluate the genotype and phenotype status of CYP2C19 in Colombian mestizos, in order to contribute to the use of appropriate strategies of drug therapy for this population.


METHODS
189 subjects were genotyped using the multiplex SNaPshot technique and a subgroup of 44 individuals received 20 mg of omeprazole followed by blood collection at 3 hours to determine the omeprazole hydroxylation index by HPLC.


RESULTS
83.6%, 15.3% and 1.1% of the subjects were genotyped as EMs, IMs and PMs, respectively. The frequencies of the CYP2C29*1 and CYP2C19*2 alleles were 91.3% and 8.7% respectively whereas the *3, *4, *5, *6 and *8 alleles were not found. No discrepancies were found between the genotype and phenotype of CYP2C19.


CONCLUSIONS
The frequency of poor metabolizers (1.1%) in the Colombian mestizos included in this study is similar to that in Bolivian mestizos (1%) but lower than in Mexican-Americans (3.2%), West Mexicans (6%), Caucasians (5%) and African Americans (5.4%). The results of this study will be useful for drug dosage recommendations in Colombian mestizos.
Isaza
Carlos
C
Grupo de Investigación en Farmacogenética, Universidad Tecnológica de Pereira, Facultad de Ciencias de la Salud, La Julita, Pereira, Colombia, South America. caisaza@utp.edu.co
Henao
Julieta
J
Martínez
José H Isaza
JH
Sepúlveda Arias
Juan C
JC
Beltrán
Leonardo
L
D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000097:blood / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D044467:American Indian or Alaska Native / Q000235:genetics*; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics* / Q000378:metabolism; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003105:Colombia; D065731:Cytochrome P-450 CYP2C19; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D006801:Humans; D006900:Hydroxylation; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics* / Q000378:metabolism; D009853:Omeprazole / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*; D010641:Phenotype; D011110:Polymorphism, Genetic
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; C049963:5-hydroxymethylomeprazole; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole