Debrisoquine polymorphismnovel CYP2D6 gene Bam HI restriction fragment length polymorphism in the Ngawbeacute; Guaymiacute; Indian of Panama

摘要

Markedly decreased cytochrome P450-mediated metabolism of debrisoquine, sparteine, and more than two dozen additional commonly prescribed drugs is an autosomal recessive trait that has been associated with several RFLP patterns involving the CYP2D6 gene. In Caucasians there are at least six variant alleles known to be correlated with the lsquo;poor metabolizerrsquo; (PM) phenotype. We examined debrisoquine and sparteine metabolism and CYP2D6 RFLP patterns in 22 Ngawbeacute; Guaymiacute; Indians of Panama. We studied a two-generation family, a three-generation family, and three other unrelated PM individuals. Digestion of all 22 DNA samples with Xba I orHindIII did not produce the same varying CYP2D6 RFLP patterns as those commonly seen in at least two-thirds of all Northern European Caucasians and Chinese so far screened. In contrast, we found a single heretofore undescribedBamHI polymorphism that was correlated with the PM phenotype among all Ngawbeacute; Guaymiacute; individuals examined. It is possible that this novel RFLP might represent a recent founder effect that has occurred in this unadmixed Amerindian tribe within the past 20 000ndash;30 000 years.