CYP2C19 is a polymorphic enzyme involved in the metabolism of clinically important drugs. Genotype-phenotype association studies of CYP2C19 have reported wide ranges in the metabolic ratios of its substrates. These discrepancies could be attributed to the variations in the promoter region and this aspect has been reported recently. The observations in the recent reports on the influence of promoter region variants on the metabolism of CYP2C19 substrates might also have been influenced by the copy number variations of CYP2C19. In this paper, we describe copy number variations of CYP2C19 using real-time polymerase chain reaction by comparative Ct method. No copy number variations were observed in the south Indian population indicating the observed discrepancies in genotype-phenotype association studies might be due to the regulatory region polymorphisms as reported earlier. 1. Introduction The CYP2C19 is a clinically important drug metabolizing enzyme encoded by polymorphic CYP2C19 gene on chromosome 10, playing a major role in metabolizing about 5% of the clinically used drugs [1–5]. Owing to genetic polymorphisms, considerable interindividual variability exists in the metabolic activity of this enzyme [6]. About 43 variant alleles of CYP2C19 have been reported till date (http://www.imm.ki.se/CYPalleles, access date: 28th March 2012). Most of the genotype-phenotype association studies of CYP2C19 in different ethnic groups were focused on exonic region variants, but the promoter region variants and copy number variations were not explored to a greater extent [7–11]. Based on the findings of genotype-phenotype association studies, subjects were categorized as poor metabolizers (PMs), having either of the most commonly seen defective alleles of CYP2C19, namely, c.636G>A (*3 allele; rs4986893) or c.681G>A (*2 allele; rs4244285); extensive metabolizers (EMs) carrying no variant alleles; ultra-rapid metabolizers (UMs) carrying ？806C>T and ？3402C>T variations (*17 allele) in the promoter region of CYP2C19 [12]. Thus, the activity of CYP2C19 varies with the presence or absence of certain variations in its gene which also varies in its distribution among different ethnic groups [8, 13–18]. CYP2C19 activity differs among extensive metabolizers (EM), demonstrated by a wide range in the metabolic ratios (MR) of probe drugs, and some discrepancies were commonly noted in these reports [11–20]. These differences could be attributed to rare defective alleles or to polymorphisms in the regulatory region of CYP2C19 gene and copy number variants of the gene [20, 21]. Few
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