Debrisoquine polymorphism: novel CYP2D6 gene Bam HI restriction fragment length polymorphism in the Ngawbé Guaymí Indian of Panama.
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 'poor metabolizer' (PM) phenotype. We examined debrisoquine and sparteine metabolism and CYP2D6 RFLP patterns in 22 Ngawbé Guaymí 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 or Hind III 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 undescribed Bam HI polymorphism that was correlated with the PM phenotype among all Ngawbé Guaymí 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 20,000-30,000 years.
Laboratory of Developmental Pharmacology, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892.
D D
DD
Petersen
A N
AN
Kong
L F
LF
Jorge
D W
DW
Nebert
T D
TD
Arias
D000483:Alleles; D005075:Biological Evolution; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D003647:Debrisoquin / Q000378:metabolism*; D005260:Female; D006801:Humans; D007197:Indians, Central American / Q000235:genetics*; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics / Q000378:metabolism; D010176:Panama; D010375:Pedigree; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D011544:Pseudogenes; D013034:Sparteine / Q000378:metabolism
D013034:Sparteine; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; D003647:Debrisoquin