PNAT AND CYP2D6 GENE POLYMORPHISM IN EPILEPTIC PATIENTS

Certain anticonvulsant drugs require N-acetylation as a major route of metabolic clearance. Single point mutations of the polymorphic N-acet yltransferase gene (pNAT) art the primary cause for impaired drug acet ylation. Pharmacokinetic parameters are altered in slow acetylator phe notypes and this may compromise drug safety. Genetic analysis of allel ic frequencies of individual pNAT genotypes point to significant incre ases in carriers of the S1/wt and S3/wt (P < 0.05) allele and a signif icant reduction in carriers of the S2/S2 (P < 0.01) allele. when contr ol and epileptic patients are compared. Furthermore, the presumed link between the cytochrome P450 CYP2D6 polymorphism and the pathogenesis of Parkinson's disease led us to investigate, whether a similar relati onship can be expected for other CNS disorders. Our findings indicate that poor metabolizers are more frequent (P < 0.05) amongst epileptic patients, when compared with a control population. An estimate of the odds ratio may suggest an increased risk [95% CI (confidence interval) 1.043-4.734] of up to 5-fold in epileptic patients carrying this muta tion. This provides further evidence for a potential link between the debrisoquine hydroxylase gene polymorphism and CNS disorder and theref ore warrants further study.