CYP2C19 genetic mutations in North Indians

Objectives: To identify defective alleles of CYP2C19 (CYP2C19*2 and *3) in North Indians. Methods: One hundred extensive metabolizers and 21 poor metabolizers of ome prazole were genotyped with respect to CYP2C19*2 and.3 alleles with polymer ase chain reaction-based diagnostic tests. Results: Fifty-two extensive metabolizers and six poor metabolizers were ho mozygous with the CYP2C19*1/*1 genotype, and 48 extensive metabolizers and six poor metabolizers were heterozygous with the CYP2C19*1/*2 genotype. Nin e poor metabolizers were homozygous with the CYP2C19*2/*2 genotype. No exte nsive or poor metabolizers demonstrated the presence of the CYP2C19*3 allel e. 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 CYP2 C19*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 m etabolizers excreted 7.85 +/- 7.6 mu mol 5-hydroxyomeprazole in 8 hours, wh ich was 28% more as compared with heterozygous extensive metabolizers who e xcreted 5.6 +/- 3.6 mu mol 5-hydroxyomeprazole in 8 hours (P < .05). Conclusions: CYP2C19*2 demonstrated allele frequency of 0.3, whereas CYP2C1 9*3 was absent in North Indians. Because CYP2C19*2 is not able to explain 5 7% of poor metabolizers, other mutations (CYP2C19*4 to *8) might be present in North Indians, CYP2C19 demonstrated differential evolution in North Ind ians because the frequency of CYP2C19*2 was similar to that in Oriental sub jects, but that of CYP2C19*3 was similar to that in white subjects.