CYP2D6 GENOTYPE DETERMINATION IN THE DANISH POPULATION

CYP2D6 genotyping was carried out by XbaI restriction fragment length polymorphism analysis and polymerase chain reaction in 168 healthy Dan ish volunteers, 77 extensive metabolizers (EM) and 91 poor metabolizer s (PM) of sparteine. All EM were genotyped correctly as heterozygous o r homozygous for the functional (wild type) gene, DG-wt. However, the DG-wt gene was apparently also present in 11 (12%) of the PM who accor dingly were incorrectly genotyped as EM. The specificity of genotyping PM thus was 100% but the sensitivity was only 88%. The most common al lele was the DG-wt with an apparent frequency of 0.741 (0.026) in the Danish population and the second most common allele was the D6-B with an apparent frequency of 0.194 (0.024). The median (range) of the spar teine metabolic ratio (MR) in 47 homozygous D6-wt EM was 0.28 (0.11-4. 10) and the corresponding value in heterozygous EM was 0.36 (0.11-9.10 ). The median difference was 0.09 (95% confidence interval: 0.02-0.16) . CYP2D6 phenotyping is a promising tool in tailoring the individual d ose of tricyclic antidepressants, some neuroleplics and some antiarrhy thmics. However if the genotype test could be improved with regard to both sensitivity in PM and the ability to predict CYP2D6 activity in E M then it would be of even greater clinical value in therapeutic drug monitoring.