CYP2C19 genetic mutations in North Indians

• Published in: Clinical pharmacology and therapeutics 2000-09, Vol.68 (3), p.328-335
• Main Authors: Lamba, Jatinder K., Dhiman, Radha K., Kohli, Krishan K.
• Format: Article
• Language: English
• Subjects: Alleles; Antisense Elements (Genetics); Aryl Hydrocarbon Hydroxylases; Biological and medical sciences; Cytochrome P-450 CYP2C19; Cytochrome P-450 Enzyme System - genetics; Female; General pharmacology; Genetics, Population; Genotype; Humans; India; Male; Medical sciences; Mixed Function Oxygenases - genetics; Omeprazole - metabolism; Pharmacokinetics. Pharmacogenetics. Drug-receptor interactions; Pharmacology. Drug treatments; Phenotype; Polymerase Chain Reaction; Polymorphism, Genetic
• ISSN: 0009-9236; 1532-6535
• DOI: 10.1067/mcp.2000.109365

Objectives To identify defective alleles of CYP2C19 (CYP2C19*2 and *3) in North Indians. Methods One hundred extensive metabolizers and 21 poor metabolizers of omeprazole were genotyped with respect to CYP2C19*2 and *3 alleles with polymerase chain reaction–based diagnostic tests. Results Fifty‐two extensive metabolizers and six poor metabolizers were homozygous with the CYP2C19*1 /*1 genotype, and 48 extensive metabolizers and six poor metabolizers were heterozygous with the CYP2C19*1/*2 genotype. Nine poor metabolizers were homozygous with the CYP2C19*2/*2 genotype. No extensive or poor metabolizers demonstrated the presence of the CYP2C19*3 allele. CYP2C19*2 could explain 43% (9/21) of the poor metabolizers and 57% (24/42) of the defective alleles in poor metabolizers. Allele frequency of CYP2C19*1 and *2 was 0.7 (95% confidence interval of 0.65 to 0.75) and 0.3 (95% confidence interval of 0.25 to 0.35), respectively. Homozygous extensive metabolizers excreted 7.85 ± 7.6 μmol 5‐hydroxyomeprazole in 8 hours, which was 28% more as compared with heterozygous extensive metabolizers who excreted 5.6 ± 3.6 μmol 5‐hydroxyomeprazole in 8 hours (P < .05). Conclusions Cyp2C19*2 demonstrated allele frequency of 0.3, whereas CYP2C19*3 was absent in North Indians. Because CYP2C19*2 is not able to explain 57% of poor metabolizers, other mutations (CYP2C19*4 to *8) might be present in North Indians. CYP2C19 demonstrated differential evolution in North Indians because the frequency of CYP2C19*2 was similar to that in Oriental subjects, but that of CYP2C19*3 was similar to that in white subjects. Clinical Pharmacology & Therapeutics (2000) 68, 328–335; doi: 10.1067/mcp.2000.109365