Inter-subject variability in therapeutic
drug response and
drug toxicity is a major problem in clinical practice. In this field genetic polymorphisms of
drug metabolizing
enzymes play an important role. In a multicenter study supported by the German Federal Institute for Drugs and Medical Devices (BfArM, Z 12.01-68502-201)
adverse drug reactions (ADRs) leading to hospital admission to departments of internal medicine have been registered and evaluated. The aim of the presented part of the study was to look for evident differences in genotypes for polymorphic
drug metabolizing
enzymes between
adverse drug reaction cases and controls. All cases found in the local area--Jena and Weimar--were genotyped for N-acetyl-
transferase 2 (NAT2), cytochrom P450 (
CYP) 2D6 and 2C19 in comparison to a control population of the same region. The investigation on genotype was carried out for about 2 years (2000-2002). 254 blood samples from patients of the ADR study were analyzed. The genotype of
drug metabolizing
enzymes was determined by means of polymerase chain reaction using allel specific primers or restriction
enzyme analysis. Within all ADRs cases genotyped, no exceptional frequencies for slow acetylators or poor metabolizers (PM) of
CYP2D6 or
CYP2C19 were found. About 65% of the individuals with ADR genotypically displayed a slow acetylator state. 6.3% PM for
CYP2D6, including
CYP2D6*3, *4 and *6 alleles, and 2.0% PM frequency for
CYP2C19 (*2) have been found in ADR cases. A direct connection between PM genotype and the ADR observed may be assumed only in few of them. Further investigations on genotype and ADR-associated drugs require a much larger sample of patients to obtain more data allowing to focus an association on specific drugs, ADR and polymorphisms genotype of
drug metabolizing
enzymes might be useful.