Optimization of cytochrome P4502D6 (CYP2D6) phenotype assignment using a genotyping algorithm based on allele frequency data

摘要: Cytochrome P4502D6 (CYP2D6) is a highly polymorphic gene locus with > 50 variant alleles which lead to wide range in enzymatic activity. So called poor metabolizers are carriers of any two non-functional the CYP2D6 gene. genotyping cumbersome and question how much necessary for an accurate phenotype prediction still debated. The goal this study was determine optimum amount required accurately predict at reasonable cost white North American population. To address issue, we designed polymerase chain reaction (PCR)/restriction fragment length polymorphism-based strategy detect 'key' mutations linked extensive metabolizer or associated combination extra-long PCR (XL-PCR). All exception deletions duplications detectable by simple restriction digestion analysis agarose gel electrophoresis. In addition, utilized algorithm based on our own published allele frequency data calculate probability correct genotype (and thus, phenotype) assignment. As little as one XL-PCR followed maximum six reamplification reactions allows individual's 99.15%. few four identify 97.9% individuals. We evaluated model 208 Americans testing presence CYP2D6*2, *3, *4, *6, *7, *8, *9, *10, *11, *12, *15, *17 *18 *5, *13 *16 deletions. For all individuals, has been predicted. Discordant assignment occurred only individuals subsequently attributed inhibition concomitant drug therapy.