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Correlation between omeprazole hydroxylase and CYP2C19 genotype in North Indians
J K Lamba1, R K Dhiman, R Singh
1Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
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.
Conclusion:
The results of the present study demonstrated concordance between the in vitro activity of OMZ hydroxylase and the CYP2C19 genotype in North Indians.
Insights
This study found a strong link between omeprazole (OMZ) hydroxylase activity in North Indians and their CYP2C19 genetic makeup. Genetic variations in CYP2C19 influence how individuals metabolize OMZ.
Area of Science:
- Pharmacogenomics
- Drug Metabolism
- Genetics
Background:
- Omeprazole (OMZ) is a widely used proton pump inhibitor.
- CYP2C19 is a key enzyme involved in OMZ metabolism.
- Genetic variations in CYP2C19 can affect drug efficacy and safety.
Purpose of the Study:
- To investigate the correlation between in vitro hepatic omeprazole (OMZ) hydroxylase activity and CYP2C19 genotype in North Indians.
- To understand the impact of CYP2C19 polymorphisms on OMZ metabolism in this population.
Main Methods:
- Liver microsomes from 15 North Indians were used to assay OMZ hydroxylase activity.
- High-performance liquid chromatography (HPLC) was employed to quantify 5-OH-OMZ.
- Genotyping for CYP2C19*2 and *3 polymorphisms was performed using PCR-based methods.
Main Results:
- Thirteen subjects were classified as extensive metabolizers (EMs) with varying OMZ hydroxylase activity.
- Homozygous CYP2C19*1/*1 individuals exhibited the highest activity.
- Two subjects identified as poor metabolizers (PMs) with CYP2C19*2/*2 genotype showed significantly reduced activity.
Conclusions:
- A clear concordance exists between in vitro OMZ hydroxylase activity and CYP2C19 genotype in North Indians.
- These findings highlight the importance of pharmacogenetics in predicting OMZ metabolism.