CANADIAN NATIVE INDIANS EXHIBIT UNIQUE CYP2A6 AND CYP2C19 MUTANT ALLELE FREQUENCIES

Many human cytochromes P450 (CYP) enzymes are polymorphically expresse d, resulting in interindividual and interethnic differences in the met abolism of substrate drugs, Little is known about the genetic variatio n of CYP enzymes in Canadian Native Indians, We therefore determined t he CYP2C19 and CYP2A6 mutant allele frequencies in 159 Canadian Native Indians and compared them with white and Asian subjects, Canadian Nat ive Indians differed significantly from both white and Asian populatio ns in allelic patterns of both CYP2C19 (19.1% CTP2C192 and 0% CYP2C19 3) and CYP2A6 (0.9% CYP2A6*2 and 13.9% CYP2A6*3). In addition, analys is of the Canadian Native Indian data suggested that there may be an a ssociation between the presence of the CYP2C19 and CYP2A6 mutant allel es such that the co-occurrence of these 2 alleles is higher than would be predicted on the basis of their individual frequencies in this pop ulation.