Research Highlights: Novel CYP2C9 Genetic Polymorphisms and Assessment of their Impact On Hydroxylation Capacity

Abstract

ISSN 1462-2416 10.2217/PGS.13.243 © 2014 Future Medicine Ltd Pharmacogenomics (2014) 15(3), 261–264 261 part of CYP2C9 is a CYP450 that constitutes approximately 20% of the total human liver microsome CYP450 protein con­ tent. CYP2C9 metabolizes approximately 10% of therapeutically important drugs such as oral sulfonylurea hypoglycemics (e.g., glimepiride, gliclazide and tolbuta­ mide), anticoagulants (e.g., warfarin and acenocoumarol), angiotensin II receptor inhibitors (e.g., losartan, irbesartan and candesartan), antiepileptics (e.g., pheny­ toin and phenobarbital) and numerous nonsteroidal anti­inflammatory drugs such as diclofenac [1,2]. The CYP2C9 gene, together with another three CYP2C genes (CYP2C8, CYP2C18 and CYP2C19), is located in a region on chromosome 10q24 [3]. This gene is highly polymorphic, including allelic variants with decreased (e.g., CYP2C9*2 or*3) or null activity (CYP2C9*6 ) [101]. The genotypic features of the CYP2C9 gene have been studied in several popula­ tions showing ethnic variability in allele distribution [2–5]. In Caucasians, the CYP2C9*1 (wild­type), *2 and *3 allelic variants are the most frequent. In Ori­ ental subjects, CYP2C9*4 has also been found, whereas in African subjects other alleles (CYP2C9*5, *6 and *8) have been identified [2–5]. In addition, a large number of SNPs have been described in the regulatory regions of the CYP2C9 gene [101], which appears to be in linkage disequilibrium with known exonic variants [6]. The studies discussed here analyze the presence of novel CYP2C9 SNPs. It appears that these genetic variations are likely to contribute to differences in CYP2C9 activ­ ity on warfarin and acenocoumarol [6,7], losartan [8] and glimepiride [9].