Molecular heterogeneity of the XbaI defined 44kb allele of the CYP2D locus within the Caucasian population.

摘要: 1. Cytochrome P450 debrisoquine (CYP2D6) activity is polymorphic and under genetic control. Most Caucasians are extensive metabolizers, but 5%-10% poor metabolizers. 2. Restriction fragment length polymorphism analysis of the CYP2D6 locus identifies a 29kb XbaI fragment, either normal (D6-wt) or mutated, three mutated alleles (44kb, 11.5kb 16 + 9kb). The 44kb allele was initially considered as metabolizer owing to D6-B mutation, cases not carrying D6-B, therefore potentially functional, have been found. degree molecular heterogeneity this investigated by phenotype genotype families. 3. Thirty-one French Caucasian families, representing 117 individuals, possessing at least one in each family were selected. Phenotypes determined using dextromethorphan, XbaI, NcoI BamH1 RFLPs 42 independent chromosomes analyzed. 4. 80% carried CYP2D6-B mutation had an additional (12.5kb 4.8kb). remaining 20% did carry A mutations no extra fragment. 5. Information on families demonstrated that associated with phenotype. 6. We conclude substantial percentage functional CYP2D gene, therefore, consistently metaboliser allele.