CYP2C9 and CYP2C19 are important drug metabolizing enzymes and together metabolize about 18% of currently available drugs. Some of the important groups of drugs that are metabolized by them are antihypertensives, hypoglycemics, anticonvulsants, antiulcer drugs etc. Genes encoding these enzymes are polymorphically expressed. Thirty variant alleles for CYP2C9 and 21 for CYP2C19 have been reported. The frequencies of these polymorphic alleles show marked inter-ethnic variation. Several reports have been published showing the clinical importance of this polymorphism. This review summarizes the currently available important information on this topic.

Aims To investigate the frequencies of CYP2C19 * 1 , CYP2C19 * 2 and CYP2C19*3 alleles and CYP2C19 genotypes in a Tamilian population. Methods The study was conducted in 112 unrelated healthy human volunteers. DNA was extracted from leucocytes and analyzed by the PCR-RFLP protocol. The PCR product was digested with restriction enzymes ( Sma I and BamH 1) and then separated electrophoretically using polyacrylamide gel.

To investigate the relationship between CYP2C19 genotypes and the hydroxylation index (HI) of omeprazole in the South Indian population. Healthy unrelated South Indian subjects (n=300) were separated into three groups based on their CYP2C19 genotypes. They were administered a single oral dose of 20 mg omeprazole, and venous blood was collected 3 h later. Plasma was assayed using reversed-phase high-performance liquid chromatography, and the omeprazole HI was calculated. The means of HIs in individuals with CYP2C19*1/*1 (n=124), *1/*2 (n=129) and *2/*2,*2/*3 (n=47) were 2.4, 5.3 and 22.5, respectively, and were found to be significantly different between any two groups (P<0.0001). A good correlation was established between CYP2C19 genotype and omeprazole HI (r=0.54, 95% CI 0.45-0.62; P<0.0001). Of the 300 subjects, 42 (14.0%; 95% CI 10.1-17.9) were phenotypic poor metabolizers (PMs), but only 33 of them had two mutant alleles and the remaining 9 PMs had at least one wild-type allele. Among the 258 extensive metabolizers, 14 had two mutant alleles. The prevalence of PMs in the South Indian population was 14.0%, which is similar to that in North Indians and Orientals but significantly higher than in Caucasians and Africans. A genotype-phenotype relationship was established between the CYP2C19 genotype and HI of omeprazole, but 7.7% of subjects deviated from expected genotype-phenotype associations. This could be due to an additional mutation, either in the exons/introns or in the 5'-regulatory region of the CYP2C19 gene.

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