Genetic polymorphism of the hepatic cytochrome P450 2C19 in North Indian subjects*

Abstract

One hundred unrelated healthy North Indian subjects were phenotyped with respect to their ability to metabolize omeprazole to 5-hydroxyomeprazole. Each volunteer was requested to ingest 20 mg (57.9 mumol) omeprazole. Urine was collected for a period of 8 hours and the amount of 5-hydroxyomeprazole excreted was estimated by HPLC. Histogram, probit, and normal test variable plots showed the antimode value for the log hydroxylation index of omeprazole to be 1.7. Of 100 North Indian subjects, 11 demonstrated log hydroxylation index values more than 1.7. Thus it is inferred that the frequency of occurrence of poor metabolizers of omeprazole in North Indian subjects is 11% (95% confidence interval, 5% to 17%). From the Hardy-Weinberg Law it was computed that the frequency of occurrence of the mutant allele of hepatic CYP2C19 in the North Indian subjects was 0.33.

Simultaneous determination of omeprazole, hydroxyomeprazole and omeprazole sulphone in human plasma by isocratic HPLC-DAD: application to the phenotyping of CYP2C19 and CYP3A4 in brazilian volunteers

“…Table 3. Precision and accuracy for the determination of HOME, OME and OMES in human plasma Spiked concentration / (ng mL 26 The prevalence of PMs in the South Indian population is 14%, being 12-23% in Orientals and 1% in Caucasians. 27 Considering the small population tested in our study, it is not possible to determine the antimode in Brazilian population.…”

“…14,[18][19][20][21][22][23][24][25] The use of DAD allows comparison of ultraviolet absorption spectra of sample peaks with reference spectra on a computer library and the determination of spectral purity of the peaks, greatly improving the specificity of the analysis. [26][27] Despite the great improvement in specificity brought to HPLC analyses by DAD, only Duboc et al 23 used a HPLC-DAD for OME determination in human plasma samples. To date, there is no report of an HPLC-DAD method for simultaneous quantification of OME, HOME and OMES in human plasma samples.…”

Prevalence of poor and rapid metabolizers of drugs metabolized by CYP2B6 in North Indian population residing in Indian national capital territory

“…However, the rates with which these drugs are metabolized vary considerably in individual hepatic microsomes, and this variation is believed to be caused by CYP2B6 isoforms, besides the environmental factors such as the enzyme inducers. Clinical importance of genetic variations and role of ethnicity of CYP2D6 , CYP2C19 , CYP2C9, and CYP2D6 are well known (Adithan et al 2003; Anitha and Banerjee 2003; Kumar et al 2010; Lamba et al 1998ab) but CYP2B6 has only recently been recognized to code for a highly variable enzyme of potential clinical importance (Lang et al 2001; Lamba et al 2003). More than 100 DNA variations have been reported in CYP2B6 gene, and many of them show extensive linkage disequilibrium giving rise to distinct haplotypes.…”

Allele frequency distribution of CYP2C19*2 allelic variants associated with clopidogrel resistance in cardiac patients

“…The present study screened Pakistani cardiac patients enrolled for clopidogrel therapy for loss-of-function alleles of CYP2C19*2, which have been observed to be involved in clopidogrel resistance in numerous ethnic groups (17)(18)(19)(20). A total of 100 cardiac patients on clopidogrel therapy were analyzed by an allele-specific extension-based SNP identification method with gel electrophoresis in this study.…”