Study of CYP2C9 and CYP2C19 polymorphisms in a Romanian epilepsy population.
2013
Introduction Patients diagnosed with epilepsy and receiving antiepileptic drug therapy can have very different responses to treatment, as well as variable risk of side effects. This variability might be partially determined by the polymorphisms of genes coding the drug-metabolizing enzymes.The CYP2C subfamily of cytochrome P450 comprises 4 members: CYP2C8, CYP2C9, CYP2C18 and CYP2C19. The genes encoding these enzymes are polymorphic. CYP2C9 hydroxylates about 15% of drugs in current clinical use. Several variants of the CYP2C9 gene have been described, but the most prevalent and most frequently studied variants are the CYP2C9*2 and CYP2C9*3 polymorphisms (Kim et al. 2004). From a clinical perspective, therapy with low therapeutic index drugs such as antivitamin K, antidiabetic sulfonamides and phenytoin can be influenced by the reduction in CYP2C9 metabolic activity, causing problems in determining the dosage or determining toxic effects (Militaru et al 2012a, b). CYP2C19 is important in the biotransformation of some anticonvulsants (S-mephenytoin and diazepam) (Ono et al 1996) but also for other important drugs, such as proton pump inhibitors, clopidogrel and antidepressants (tricyclic antidepressants and selective serotonin reuptake inhibitors)(Gardiner & Begg 2006). The estimated fraction of responsibility for drug metabolism in phase 1 reactions for CYP2C19 is 5%. Seven variants (*2–*8) in the CYP2C19 gene have been associated with reduced enzyme activity in vivo, largely due to production of inactive enzyme protein (Ingelman-Sundberg et al 2005). The most common variants are *2 and *3. However, the CYP2C19*17 variant is associated with an ultrarapid metabolism phenotype (Sim et al 2006). This study is designed to determine the distribution of CYP2C9 and CYP2C19 polymorphisms in a Romanian epileptic population and to make a comparison between the population with epilepsy and a healthy population, regarding the distribution of the major mutant alleles that determine the poor-metabolizer status.
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