Correlation between omeprazole hydroxylase and CYP2C19 genotype in North Indians.
OBJECTIVE
To comprehend the correlation between the in vitro activity of hepatic omeprazole (OMZ) hydroxylase and genotype of North Indians with respect to CYP2C19.


METHODS
Microsomes were prepared from the livers of 15 North Indians. Assay of OMZ hydroxylase was performed by incubating the microsomes with OMZ in the presence of reduced nicotinamide adenine dinucleotide phosphate (NADPH). The 5-OH-OMZ formed was assayed using high-performance liquid chromatography. Genomic DNA isolated from the blood of the same individuals was employed for genotyping of CYP2C19*2 and *3 using polymerase chain reaction-based diagnostic tests.


RESULTS
Thirteen subjects demonstrated an average OMZ hydroxylase activity of 138 pmol 5-OH-OMZ formed/min/mg protein. They were designated as extensive metabolisers (EMs). Eight EMs were homozygous with CYP2C19*1/*1 genotype and demonstrated the highest average activity of OMZ hydroxylase (169 pmol 5-OH-OMZ formed/min/mg protein). Five heterozygous EMs (CYP2C19*1/*2) demonstrated 52% activity of OMZ hydroxylase compared with eight homozygous EMs (CYP2CI9*1/*1). Two subjects demonstrated 11% activity of OMZ hydroxylase (15 pmol 5-OH-OMZ formed/min/mg protein) compared with EMs. Hence, these individuals were designated as poor metabolisers (PMs). Both PMs had genotype CYP2C19*2/*2. None of the subjects had CYP2C19*3/*3 genotype.


CONCLUSIONS
The results of the present study demonstrated concordance between the in vitro activity of OMZ hydroxylase and the CYP2C19 genotype in North Indians.
Lamba
J K
JK
Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Dhiman
R K
RK
Singh
R
R
Kohli
K K
KK
D000483:Alleles; D001189:Aryl Hydrocarbon Hydroxylases; D002851:Chromatography, High Pressure Liquid; D065731:Cytochrome P-450 CYP2C19; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism*; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D007194:India; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D009853:Omeprazole / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic
D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D009853:Omeprazole