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CYP2C19 genetic mutations in North Indians
J K Lamba1, R K Dhiman, K K Kohli
1Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Clinical Pharmacology and Therapeutics
|October 3, 2000
Summary
The CYP2C19*2 allele is common in North Indians, while CYP2C19*3 is absent. Other genetic variations likely contribute to omeprazole metabolism differences in this population.
Area of Science:
- Pharmacogenomics
- Genetic variations in drug metabolism
Background:
- Cytochrome P450 2C19 (CYP2C19) is crucial for metabolizing drugs like omeprazole.
- Genetic polymorphisms in CYP2C19 influence drug efficacy and safety.
- Understanding allele frequencies in diverse populations is essential for personalized medicine.
Purpose of the Study:
- To identify and quantify the prevalence of defective CYP2C19 alleles (*2 and *3) in a North Indian population.
- To correlate CYP2C19 genotype with omeprazole metabolic phenotype.
Main Methods:
- Genotyping of 121 individuals (100 extensive and 21 poor metabolizers of omeprazole) using polymerase chain reaction (PCR).
- Analysis focused on identifying CYP2C19*2 and CYP2C19*3 alleles.
- Phenotyping based on omeprazole metabolism and 5-hydroxyomeprazole excretion.
Main Results:
- CYP2C19*2 allele frequency was found to be 0.3 in the North Indian cohort.
- The CYP2C19*3 allele was absent in all studied individuals.
- CYP2C19*2 accounted for 43% of poor metabolizers, indicating other genetic factors are involved.
- Significant differences in 5-hydroxyomeprazole excretion were observed between homozygous and heterozygous extensive metabolizers.
Conclusions:
- CYP2C19*2 is a significant determinant of omeprazole metabolism in North Indians, with a frequency comparable to Oriental populations.
- The absence of CYP2C19*3 suggests a distinct genetic evolutionary pattern compared to white populations.
- The significant proportion of poor metabolizers not explained by CYP2C19*2 highlights the potential role of other unidentified CYP2C19 variants (e.g., *4-*8) in this population.