GENETIC-BASIS FOR DIFFERENCES IN DEBRISOQUIN POLYMORPHISM BETWEEN A SPANISH AND OTHER WHITE-POPULATIONS

The debrisoquin hydroxylation polymorphism is an autosomic recessive trait of the cytochrome P450IID6, an enzyme involved in drug metabolism, that affects 5% to 10% of white subjects. The genetic basis of this polymorphism was studied in 258 unrelated Spanish white subjects. The results revealed that about 5% of the subjects were homozygous for mutant alleles and that about 1% of the subjects carried alleles that suggested CYP2D6 gene duplication. The extensive metabolizers who were homozygous for the wild-type allele had higher metabolic ratio than the heterozygous extensive metabolizers, indicating a gene-dose effect for the wild type allele. The CYP2D6 allele frequencies indicate a reduced frequency for the CYP2D6(B) allele and a higher frequency for the wild-type allele compared with other white populations. This is also reflected in an increased frequency of the subjects who were homozygous for the wild-type allele among extensive metabolizers. We conclude that the same CYP2D6 mutations are present in Spaniards and other white subjects. Nevertheless, the frequencies of such mutations are different in our population. This implies that a high number of Spanish subjects may behave differently than other white subjects in the effect of drugs metabolized by the CYP2D6 enzyme.